Contributed equally
Desmoplastic melanoma (DM) is a rare morphological subtype of melanoma that remains uncharacterized. The aim of the present study was to investigate the incidence of DM, its general demographics, clinicopathological features and disease-specific prognostic factors. DM cases were sampled from the Surveillance, Epidemiology and End Results (SEER) program from between 1973 and 2017. A total of 3,657 cases (median age, 68 years) were identified. The results indicated that DM primarily occurred in Caucasian subjects, with a male-to-female ratio of 2:1. Statistically significant overall survival (OS) and disease-specific survival (DSS) rate differences were identified according to sex, age, treatment, T stage, N stage and SEER historic tumor stage (P<0.05). In multivariate Cox regression analysis, age >68 years, male sex, American Joint Committee on Cancer (AJCC) stage II and III, and SEER historic tumor stage of the regional tumor were all factors associated with poorer OS and DSS rates. The findings also revealed that surgical treatment was associated with favorable DSS and OS rates. In conclusion, DM occurred primarily in Caucasian subjects of 60–80 years of age, with predominance in males. Furthermore, age, sex, AJCC stage, SEER historic tumor stage and surgical treatment were identified as independent prognostic factors of DM in terms of DSS and OS.
Desmoplastic melanoma (DM) was first reported in 1971 as a rare morphological variant of melanoma composed of spindle melanocytes and abundant collagen (
DM differs from traditional melanomas in clinical presentation (
According to previously reported statistics based on Surveillance, Epidemiology, and End Results (SEER) studies in the USA, DM accounts for ~4% of all melanoma cases and its incidence rate was ~2×10−6%, which steadily increased between 1992 and 2013 (
Data from the present study is publicly available from the SEER program (
Overall statistical analysis was performed using SPSS for Windows (version 23.0; IBM Corp., Armonk, IL, USA). A χ2 test was used to examine bivariate associations between categorical variables. Melanoma-specific and all-cause mortality rates were investigated. The primary endpoint was considered to be the date of DM-associated mortality. The time point between the date of diagnosis and the date of DM-associated mortality was defined as the disease-specific survival (DSS). Kaplan-Meier survival analyses with log-rank tests were used to estimate survival. Furthermore, Cox proportional hazards regression was used to estimate the hazard ratio. All statistical tests were two-tailed. P-values were two-sided. P<0.05 was considered to indicate a statistically significant difference.
The primary aim of the present study was to determine the general demographics, incidence and tumor-specific clinicopathological features of DM.
Kaplan-Meier analysis was utilized for time-to-event analysis of overall survival (OS) and DSS rates. OS analysis was performed by stratifying different demographic and clinicopathological features of DM. Statistically significant differences were identified with regard to sex (female vs. male, P<0.001), age (≤68 vs. >68 years, P<0.001), AJCC stage (I+II vs. III+IV, P<0.001), SEER historic tumor stage (localized + regional vs. distant metastasis tumor, P<0.001), T stage (TX+T1+T2 vs. T3+T4, P<0.001; based on the Tumor-Node-Metastasis staging system (
A Cox proportional hazards regression model was constructed to evaluate predictors of OS and DSS (
In the multivariate analysis, age >68 years old (OS and DSS, P<0.001), male sex (OS, P<0.001; DSS, P=0.005), AJCC stage II and III (OS for stage II and III, P<0.001; DSS for stage II, P=0.009; and DSS for stage III, P<0.001) and SEER historic tumor stage (OS, P<0.001; DSS, P=0.009) were associated with poorer OS and DSS rates. Notably, surgical treatment was associated with favorable DDS and OS rates (OS, P<0.001S; DSS, P=0.015;
DM is a rare variant of melanoma that can be easily misdiagnosed. Clinically, the appearance of DM is often nonspecific and amelanotic (
The present study indicated that the presentation of DM was associated with increased age. Notably, the incidence of DM was highest in the 6-8th decade of life, with predominance in males. Furthermore, the present findings revealed that DM primarily originated from the skin. Of note, people of Caucasian ethnicity accounted for the majority of the study population. This is in accordance with previous studies (
One of the main aims of the present study was to identify prognostic factors in patients with DM. The results demonstrated that sex and age were independent prognostic factors for DSS and OS. These results are in accordance with previous studies (
Since DM has a low rate of nodal metastasis, investigators have suggested that routine sentinel node biopsy may be not necessary (
Previous studies have demonstrated that DM had a propensity for local recurrence and distant metastasis, particularly with regard to the ‘pure’ DM subtype (
Previous studies have suggested that surgical margins are critical in the management of DM local recurrence and that wide surgical resection margins are required (
In conclusion, use of the National Cancer Institute SEER registries in the present study extended the current knowledge of DM. The large number of patients enabled description of the demographic and clinicopathological features and disease-specific prognostic factors of DM. Compared with other studies, a notable strength of the present study was its robust long-term follow-up assessment of survival provided by the SEER database. However, there were several limitations of the current study. Notably, the study could not differentiate between the DM subtypes. This was because the SEER registry is coded according to the final diagnosis obtained from a pathology report and only applied the ICD-O-3 morphology code for all types of DM. In addition, not all cases had complete information, and these missing data undoubtedly weaken the strength of the current investigation. As aforementioned, certain important prognostic data, including pathological grade, surgical types, margin status and adjuvant therapies, were either absent or incomplete in the SEER database. Therefore, the influences of these factors on the overall prognosis could not be assessed. In addition, the patients with DM represented an older population and there was a lack of comorbidity data, which may significantly affect treatment protocol and outcomes.
In conclusion, to the best of our knowledge, the present study is the first to report on a large case series concerning the demographics, clinicopathological features and disease-specific prognostic factors of DM. The results demonstrated that DM primarily occurred in Caucasians, with a predominance in males, and the highest incidence occurred in the 6-8th decades of life. Age, sex, AJCC stage, SEER historic stage and surgical treatment were identified as independent prognostic factors for DSS and OS rates.
Not applicable.
The present study was supported by The Scientific Research Foundation of Shanghai Stomatological Hospital, Fudan University (Shanghai, China; grant no. SSDCZ-2016-01).
The datasets generated during the present study are available in the official software SEER*Stat v.8.3.4 repository (
ZX and PS were major contributors in writing the manuscript. PS designed the experiments, wrote the original draft and revised the manuscript. ZX was responsible for analysis of the data and revising the manuscript. XL and FY collected and interpreted patient data. AW was responsible for planning, organizing, checking the data and the manuscript throughout the project. All authors read and approved the final manuscript.
Due to the retrospective nature of this study, it was granted an exemption in writing by the University of Fudan Institutional Review Board (Shanghai, China).
Not applicable.
The authors declare that they have no competing interests.
desmoplastic melanoma
overall survival
disease-specific survival
Surveillance, Epidemiology and End Results
American Joint Committee on Cancer
Age and sex distributions of patients with desmoplastic melanoma.
Kaplan-Meier curves for overall survival rate. Kaplan-Meier curves for overall survival according to (A) age, (B) sex, (C) AJCC stage, (D) SEER historic tumor stage, (E) T stage, (F) N stage, (G) M stage, (H) treatment, (I) tumor location and (J) ethnicity. T, tumor; N, node; M, metastasis; SEER, Surveillance, Epidemiology and End Results AJCC, American Joint Committee on Cancer.
Kaplan-Meier curves for disease-specific survival rate. Kaplan-Meier curves for disease-specific survival according to (A) age, (B) sex, (C) SEER historic tumor stage, (D) treatment, (E) T stage and (F) N stage. T, tumor; N, node; SEER, Surveillance, Epidemiology and End Results.
Baseline characteristics of desmoplastic melanoma cases in the SEER database.
Overall survival | Melanoma-specific survival | |||||
---|---|---|---|---|---|---|
Characteristics | Alive | Dead | P-value | Alive | Dead | P-value |
Age, years | <0.001 | – | ||||
≤68 | 1,278 | 320 | 689 | 137 | ||
>68 | 947 | 1,112 | 0 | 0 | ||
Sex | <0.001 | <0.001 | ||||
Female | 807 | 374 | 321 | 41 | ||
Male | 1,418 | 1,058 | 368 | 96 | ||
Ethnicity | 0.026 | 0.995 | ||||
Caucasian | 2,149 | 1,403 | 655 | 130 | ||
African descent | 15 | 9 | 10 | 2 | ||
Other | 61 | 20 | 24 | 5 | ||
Tumor site | 0.014 | 0.548 | ||||
Internal organs | 1 | 2 | 1 | 0 | ||
Nose and mouth | 7 | 6 | 5 | 0 | ||
Skin | 2,217 | 1,418 | 683 | 137 | ||
Other | 0 | 6 | 0 | 0 | ||
Grade | 0.216 | 0.451 | ||||
I | 1 | 2 | 0 | 0 | ||
II | 6 | 3 | 2 | 0 | ||
III | 10 | 15 | 2 | 1 | ||
IV | 5 | 4 | 1 | 1 | ||
Unknown | 2,203 | 1,408 | 686 | 135 | ||
AJCC stage | <0.001 | <0.001 | ||||
I | 663 | 178 | 187 | 15 | ||
II | 792 | 383 | 184 | 26 | ||
III | 68 | 44 | 23 | 11 | ||
IV | 25 | 50 | 12 | 3 | ||
T stage | <0.001 | 0.073 | ||||
T0 | 6 | 8 | 2 | 0 | ||
T1 | 365 | 109 | 107 | 11 | ||
T2 | 376 | 106 | 104 | 8 | ||
T3 | 387 | 171 | 94 | 10 | ||
T4 | 455 | 275 | 109 | 25 | ||
TX | 116 | 64 | 33 | 4 | ||
N stage | <0.001 | 0.012 | ||||
N0 | 1,572 | 628 | 405 | 44 | ||
N1 | 47 | 38 | 19 | 7 | ||
N2 | 22 | 15 | 6 | 2 | ||
NX | 64 | 52 | 19 | 5 | ||
M stage | <0.001 | <0.001 | ||||
M0 | 1,654 | 660 | 465 | 59 | ||
M1 | 23 | 51 | 169 | 53 | ||
MX | 28 | 22 | 1 | 0 | ||
SEER stage | <0.001 | <0.001 | ||||
Localized | 1,486 | 710 | 465 | 59 | ||
Regional | 603 | 562 | 169 | 53 | ||
Distant | 4 | 7 | 1 | 0 | ||
Unstaged | 77 | 50 | 33 | 9 | ||
Treatment | 0.017 | 0.075 | ||||
Non-surgery | 67 | 69 | 19 | 3 | ||
Surgery | 2,156 | 1,361 | 670 | 133 |
SEER, Surveillance, Epidemiology and End Results; AJCC, American joint committee on cancer; T, tumor; N, node; M, metastasis; TX, T stage unknown; NX, N stage unknown; MX, M stage unknown.
Univariate Cox regression analysis of clinicopathological parameters in desmoplastic melanoma for DSS and OS.
OS | DSS | |||
---|---|---|---|---|
Parameters | HR (95% CI) | P-value | HR (95% CI) | P-value |
Age, years | ||||
≤68 | 1.0 (Reference) | 1.0 (Reference) | ||
>68 | 4.595 (4.043–5.223) | <0.001 | 3.083 (2.517–3.777) | <0.001 |
Ethnicity | ||||
Caucasian | 1.0 (Reference) | 1.0 (Reference) | ||
African descent | 0.747 (0.388–1.438) | 0.382 | 0.880 (0.329–4.129) | 0.800 |
Other | 0.566 (0.364–0.880) | 0.011 | 0.452 (0.187–1.093) | 0.078 |
Sex | ||||
Female | 1.0 (Reference) | 1.0 (Reference) | ||
Male | 1.639 (1.456–1.844) | <0.001 | 1.808 (1.448–2.258) | <0.001 |
Tumor location | ||||
Internal organs | 1.0 (Reference) | 1.0 (Reference) | ||
Nose and mouth | 0.793 (0.160–3.934) | 0.777 | 0.615 (0.056–6.788) | 0.691 |
Skin | 0.464 (0.116–1.858) | 0.278 | 0.311 (0.044–2.218) | 0.244 |
Other site | 2.839 (0.573–14.079) | 0.201 | 35.024 (3.047–402.601) | 0.004 |
Grade | ||||
I | 1.0 (Reference) | 1.0 (Reference) | ||
II | 0.650 (0.109–3.892) | 0.637 | 0.485 (0.030–7.761) | 0.609 |
III | 2.563 (0.568–11.212) | 0.211 | 1.791 (0.209–15.343) | 0.595 |
IV | 1.060 (0.194–5.788) | 0.946 | 1.045 (0.095–11.252) | 0.971 |
Unknown | 0.719 (0.180–2.879) | 0.641 | 0.468 (0.066–3.333) | 0.449 |
AJCC stage | ||||
I | 1.0 (Reference) | 1.0 (Reference) | ||
II | 1.693 (1.417–2.022) | <0.001 | 2.031 (1.422–2.901) | <0.001 |
III | 2.570 (1.847–3.577) | <0.001 | 5.693 (3.444–9.412) | <0.001 |
IV | 6.210 (4.533–8.509) | <0.001 | 11.207 (6.571–19.113) | <0.001 |
T stage | ||||
T0 | 1.0 (Reference) | 1.0 (Reference) | ||
T1 | 0.281 (0.137–0.577) | 0.001 | 1.800 (0.414–7.831) | 0.433 |
T2 | 0.252 (0.123–0.517) | <0.001 | 0.452 (0.239–0.855) | 0.015 |
T3 | 0.384 (0.189–0.781) | 0.008 | 0.484 (0.2630.891) | 0.020 |
T4 | 0.521 (0.258–1.052) | 0.069 | 0.779 (0.441–1.379) | 0.392 |
TX | 0.428 (0.205–0.891) | 0.024 | 1.329 (0.783–2.254) | 0.292 |
N stage | ||||
N0 | 1.0 (Reference) | 1.0 (Reference) | ||
N1 | 1.958 (1.41–2.717) | <0.001 | 3.297 (2.050–5.301) | <0.001 |
N2 | 2.255 (1.351–3.764) | <0.001 | 5.364 (2.632–10.929) | <0.001 |
NX | 1.791 (1.350–2.377) | <0.001 | 2.591 (1.612–4.615) | <0.001 |
M stage | ||||
M0 | 1.0 (Reference) | <0.001 | 1.0 (Reference) | |
M1 | 4.533 (3.407–6.033) | <0.001 | 7.114 (4.527–11.181) | <0.001 |
MX | 1.185 (0.774–1.813) | 0.434 | 0.773 (0.287–2.084) | 0.611 |
SEER stage | ||||
Localized | 1.0 (Reference) | 1.0 (Reference) | ||
Regional | 1.816 (1.625–2.029) | <0.001 | 2.345 (1.890–2.9120) | <0.001 |
Distant | 10.773 (5.098–22.767) | <0.001 | 8.951 (1.249–64.162) | 0.029 |
Unstaged | 1.212 (0.910–1.615) | 0.189 | 1.127 (0.595–2.134) | 0.714 |
Treatment | ||||
Non-surgery | 1.0 (Reference) | 1.0 (Reference) | ||
Surgery | 0.498 (0.391–0.634) | <0.001 | 0.428 (0.273–0.671) | <0.001 |
SEER, Surveillance, Epidemiology and End Results; AJCC, American joint committee on cancer; T, tumor; N, node; M, metastasis; TX, T stage unknown; NX, N stage unknown; MX, M stage unknown.
Multivariate Cox regression analysis of clinicopathological parameters in desmoplastic melanoma for DSS and OS.
OS | DSS | |||
---|---|---|---|---|
Parameters | HR (95% CI) | P-value | HR (95% CI) | P-value |
Age, years | ||||
≤68 | 1.0 (Reference) | 1.0 (Reference) | ||
>68 | 4.225 (3.454–5.242) | <0.001 | 3.055 (2.204–4.235) | <0.001 |
Sex | ||||
Female | 1.0 (Reference) | 1.0 (Reference) | ||
Male | 1.465 (1.207–1.777) | <0.001 | 1.673 (1.169–2.392) | 0.005 |
AJCC stage | ||||
I | 1.0 (Reference) | 1.0 (Reference) | <0.001 | |
II | 1.434 (1.174–1.750) | <0.001 | 1.716 (1.145–2.572) | 0.009 |
III | 2.305 (1.578–3.367) | <0.001 | 4.180 (2.252–7.756) | <0.001 |
IV | 0.001 (0.000–1.037) | 0.948 | 0.000 (0.000–5.328) | 0.965 |
SEER historic stage | ||||
Localized | 1.0 (Reference) | 1.0 (Reference) | ||
Regional | 1.467 (1.215–1.770) | <0.001 | 1.615 (1.127–2.315) | 0.009 |
Distant | 1.937 (0.528–3.392) | 0.932 | 1.827 (0.392–5.874) | 0.952 |
Treatment | ||||
Non-surgery | 1.0 (Reference) | 1.0 (Reference) | ||
Surgery | 0.317 (0.199–0.504) | <0.001 | 0.234 (0.073–0.751) | 0.015 |
OS, overall survival; DSS, disease-specific survival; SEER, Surveillance, Epidemiology and End Results; AJCC, American Joint Committee on Cancer; HR, hazard ratio; CI, confidence interval.