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Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (2): 262-269. doi: 10.19723/j.issn.1671-167X.2023.02.009

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Clinicopathological features and prognosis of anorectal melanoma: A report of 68 cases

Yu-mei LAI1,Zhong-wu LI1,*(),Huan LI2,Yan WU1,Yun-fei SHI1,Li-xin ZHOU1,Yu-tong LOU1,Chuan-liang CUI3   

  1. 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China
    2. Department of Pathology, Beijing Tsinghua Changgung Hospital; School of Clinical Medicine, Tsinghua University; Beijing 102218, China
    3. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing 100142, China
  • Received:2022-10-13 Online:2023-04-18 Published:2023-04-12
  • Contact: Zhong-wu LI E-mail:zhwuli@hotmail.com

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Abstract:

Objective: To investigate the clinicopathological characteristics of anorectal mucosal melanoma (ARMM), and to evaluate the prognostic factors. Methods: A total of 68 primary ARMM surgical specimens from 2010 to 2018 were retrospectively studied. Slides were reviewed to evaluate pathological features. Slingluff staging method was used for staging. Results: (1) Clinical features: The median age at diagnosis in this group was 61.5 years, with a male-to-female ratio 1 ∶1.62. The most common complaint was blooding (49 cases). For anatomic site, anorectum was the prevalent (66.2%), followed by rectum (20.6%). At the time of diagnosis, 28 cases were stage Ⅰ (localized stage, 41.2%), 25 cases were stage Ⅱ (regional lymph node metastasis, 36.8%), and 15 cases were stage Ⅲ (distant metastasis, 22.1%). Five patients underwent wide local excision, the rest abdominoperineal resection, and 48 patients received adjuvant therapy after surgery. (2) Pathological features: Grossly 88.2% of the tumors were exophytic polypoid masses, with the median tumor size 3.5 cm and the median tumor thickness 1.25 cm. Depth of invasion below lamina muscularis mucosae ranged from 0-5.00 cm (median 1.00 cm). The deepest site of tumor invasion reached muscular layer in 27 cases, and perirectal tissue in 16 cases. Melanin pigmentation was absent or not obvious in 67.6% of the cases. The predominant cytology was epithelioid (45 cases, 66.2%). The rate for ulceration, necrosis, lymphovascular invasion, and perineural invasion was 89.7%, 35.3%, 55.9%, and 30.9%, respectively. The median mitotic count was 18/mm2. The positive rate of S100, HMB-45 and Melan-A were 92.0%, 92.6% and 98.0%, respectively. The median of Ki-67 was 50%. The incidences of mutations within CKIT, BRAF and NRAS genes were 17.0% (9 cases), 3.8% (2 cases) and 9.4% (5 cases), respectively. (3) Prognosis: Survival data were available in 66 patients, with a median follow-up of 17 months and a median survival time of 17.4 months. The 1-year, 2-year and 5-year overall survival rate was 76.8%, 36.8% and 17.2%, respectively. The rate of lymphatic metastasis at diagnosis was 56.3%. Forty-nine patients (84.5%) suffered from distant metastasis, and the most frequent metastatic site was liver. Univariate analysis revealed that tumor size (>3.5 cm), depth of invasion below lamina muscularis mucosae (>1.0 cm), necrosis, lymphovascular invasion, BRAF gene mutation, lack of adjuvant therapy after surgery, deep site of tumor invasion, and high stage at diagnosis were all poor prognostic factors for overall survival. Multivariate model showed that lymphovascular invasion and BRAF gene mutation were independent risk factors for lower overall survival, and high stage at diagnosis showed borderline negative correlation with overall survival. Conclusion: The overall prognosis of ARMM is poor, and lymphovascular invasion and BRAF gene mutation are independent factors of poor prognosis. Slingluff staging suggests prognosis effectively, and detailed assessment of pathological features, clear staging and genetic testing should be carried out when possible. Depth of invasion below lamina muscularis mucosae of the tumor might be a better prognostic indicator than tumor thickness.

Key words: Mucosal melanoma, Anorectal tumor, Clinicopathological features, Prognosis

CLC Number: 

  • R735.3

Table 1

Clinicopathological features of 68 anorectal melanoma cases"

Features Value Features Value
Gender Pigmentation
    Male 26 (38.2%)     Obvious 22 (32.4%)
    Female 42 (61.8%)     Not obvious 46 (67.6%)
Age/years Cytology*
    Median (range) 61.5 (43.0-99.0)     Epithelioid 45 (66.2%)
Anatomic site     Spindled 19 (27.9%)
    Rectum 14 (20.6%)     Nevoid 22 (32.4%)
    Anorectum 45 (66.2%)     Polymorphic 7 (10.3%)
    Anal canal 9 (13.2%) Ulceration
Stage at diagnosis     Yes 61 (89.7%)
    Ⅰ 28 (41.2%)     No 7 (10.3%)
    Ⅱ 25 (36.8%) Necrosis
    Ⅲ 15 (22.1%)     Yes 24 (35.3%)
Therapy     No 44 (64.7%)
    Surgery only 20 (29.4%) Lymphovascular invasion
    Adjuvant therapy after surgery 48 (70.6%)     Yes 38 (55.9%)
Surgery     No 30 (44.1%)
    WEL 6 (8.8%) Perineural invasion
    APR 62 (91.2%)     Yes 21 (30.9%)
Tumor size/cm     No 47 (69.1%)
    Median (range) 3.5 (0.5-8.5) Mitosis (per mm2)
    ≤2.0 13 (19.1%)     Median (range) 18 (2-59)
    2.1-4.0 33 (48.5%)     ≤10 17 (25.0%)
    4.1-6.0 14 (20.6%)     11-20 26 (38.2%)
    ≥6.1 8 (11.8%)     21-30 14 (20.6%)
Tumor thickness/cm     ≥31 11 (16.2%)
    Median (range) 1.25 (0.06-5.00) TILs
    ≤1.0 24 (35.3%)     Brisk 9 (13.2%)
    1.1-2.0 38 (55.9%)     Non-brisk 59 (86.8%)
    ≥2.1 6 (8.8%) Ki-67 (32 cases)
Depth of invasion below lamina muscularis mucosae/cm     Median(range) 50% (10%-90%)
    Median (range) 1.0 (0-5.0) Gene mutations (53 cases)
    ≤1.0 35 (51.5%) CKIT mutation 9 (17.0%)
    1.1-2.0 29 (42.6%) BRAF mutation 2 (3.8%)
    ≥2.1 4 (5.9%) NRAS mutation 5 (9.4%)
Deepest site of tumor invasion     Wild types 37 (69.8%)
    Lamina propria 2 (2.9%)
    Submucosa 23 (33.8%)
    Muscular layer 27 (39.7%)
    Perirectal tissue 16 (23.5%)

Figure 1

Overall survival curve of 66 patients with anorectal melanoma    Figure 2    Univariate analysis of some characteristics associated with overall survival in 66 patients with anorectal melanoma 2A, stage at diagnosis; 2B, deepest site of tumor invasion; 2C, tumor size; 2D, depth of invasion below lamina muscularis mucosae; 2E, lymphovascular invasion; 2F, genetic mutations; 2G, adjuvant therapy after surgery."

Table 2

Univariate analysis of prognostic factors of overall survival in 66 patients with anorectal melanoma"

Features No. of cases No. of death Median survival/months 95%CI χ2 P value
All patient 66 53 17.433 16.198-18.668
Gender
    Male 26 21 19.300 5.203-33.397
    Female 40 32 16.733 14.090-19.377 0.168 0.682
Age
    ≤61.5 years old 33 27 19.000 13.130-24.870
    >61.5 years old 33 26 16.633 11.607-21.659 0.240 0.624
Anatomic site
    Rectum 12 8 12.933 6.926-18.940
    Anorectum 45 37 16.733 12.479-20.988
    Anal canal 9 8 34.667 29.115-40.218 0.669 0.716
Stage at diagnosis
    Ⅰ 27 18 33.300 8.835-57.765
    Ⅱ 24 22 16.733 10.672-22.794
    Ⅲ 15 13 12.333 10.113-14.554 13.226 0.001*
Therapy
    Surgery only 18 17 14.100 8.326-19.874
    Adjuvant therapy after surgery 48 36 19.000 10.371-27.629 7.361 0.007*
Surgery
    WEL 6 4 18.533 12.652-24.415
    APR 60 49 17.267 15.003-19.531 0.687 0.407
Tumor size
    ≤3.5 cm 36 25 29.033 9.522-48.545
    >3.5 cm 30 28 12.933 11.934-13.933 8.607 0.003*
Tumor thickness
    ≤1.25 cm 32 25 21.700 16.196-27.204
    >1.25 cm 34 28 13.100 12.032-14.168 1.494 0.222
Depth of invasion below lamina muscularis mucosae
    ≤1.0 cm 34 23 32.767 16.767-48.766
    >1.0 cm 32 30 12.767 11.736-13.797 13.189 < 0.001*
Deepest site of tumor invasion
    Lamina propria or submucosa 25 14 34.667 15.019-54.314
    Muscular layer 25 24 17.433 14.822-20.045
    Perirectal tissue 16 15 11.067 6.940-15.193 27.037 < 0.001*
Pigmentation
    Not obvious 44 33 19.000 12.744-25.256
    Obvious 22 20 13.533 6.041-21.026 2.804 0.094
Ulceration
    Yes 59 47 17.267 15.024-19.510
    No 7 6 42.133 18.096-66.170 1.072 0.300
Necrosis
    Yes 23 21 12.933 11.828-14.038
    No 43 32 25.100 10.006-40.194 20.243 < 0.001*
Lymphovascular invasion
    Yes 37 34 13.533 8.783-18.284
    No 29 19 32.767 18.918-46.616 10.003 0.002*
Perineural invasion
    Yes 21 19 12.933 11.692-14.175
    No 45 34 19.000 17.128-20.872 3.171 0.075
Mitosis
    ≤18/mm2 35 27 22.467 13.117-31.816
    >18/mm2 31 26 13.533 9.084-17.983 3.855 0.050
TILs
    Brisk 8 8 18.333 10.387-26.279
    Non-brisk 58 45 17.267 14.467-20.066 0.146 0.703
Ki-67 (31 cases)
    ≤50% 17 14 18.533 14.027-23.040
    >50% 14 9 29.033 0.000-58.490 1.587 0.208
Gene mutations (52 cases)
    CKIT mutation 8 7 17.267 9.505-25.028
    BRAF mutation 2 2 3.700
    NRAS mutation 5 5 16.200 9.186-23.214
    Wild types 37 28 18.333 14.651-22.016 32.244 < 0.001*

Table 3

Multivariate analysis of prognostic factors of overall survival in 66 patients with anorectal melanoma"

Features HR value 95%CI P value
Stage at diagnosis
    Ⅱ vs. Ⅰ 1.995 0.742-5.362 0.171
    Ⅲ vs. Ⅰ 2.790 0.941-8.272 0.064
Therapy (adjuvant therapy after surgery vs. surgery only) 0.647 0.282-1.482 0.303
Tumor size (>3.5 cm vs. ≤3.5 cm) 1.755 0.796-3.872 0.164
Depth of invasion below lamina muscularis mucosae (>1.0 cm vs.≤1 cm) 1.027 0.407-2.592 0.954
Deepest site of tumor invasion 1.091 0.573-2.075 0.791
    Muscular layer vs. lamina propria or submucosa 1.332 0.535-3.316 0.538
    Perirectal tissue vs. lamina propria or submucosa 1.542 0.383-6.203 0.542
Lymphovascular invasion (yes vs. no) 2.929 1.261-6.804 0.012
Gene mutations
    CKIT mutation vs. wild types 1.543 0.576-4.132 0.388
    BRAF mutation vs. wild types 110.292 12.244-993.515 < 0.001
    NRAS mutation vs. wild types 2.311 0.731-7.311 0.154
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