Key points Questions Should primary cutaneous melanomas with features suggestive of impending ulceration be classified as ulcerated or non-ulcerated, as defined by the American Joint Committee on Cancer (AJCC)? Findings This retrospective case-control study of 340 melanoma patients found that tumors with incipient ulceration were significantly thicker and more mitotically active than non-ulcerated controls, and significantly more likely to have lymphovascular invasion, positive sentinel nodes, and satellite lesions. Meaning These findings suggest that primary melanomas with incipient ulceration may be more biologically aggressive than nonulcerated melanomas, and that pathologists should note the presence of incipient ulceration until a future AJCC guideline clarifies the classification. |
Importance
Ulceration represents a key feature in cutaneous melanoma and contributes to staging according to the current American Joint Committee on Cancer (AJCC) system . However, cases with incipient ulceration do not fully meet the AJCC definition of ulceration and are consequently classified as non-ulcerated , presenting interpretation difficulties for pathologists. The prognostic implication of incipient ulceration is uncertain.
Aim
To evaluate the prognostic significance of incipient ulceration in cutaneous melanoma.
Design, environment and participants
This case-control study consisted of resected primary cutaneous melanomas diagnosed between 2005 and 2015, identified in the Melanoma Institute Australia research database and with slides available for review at the Royal Prince Alfred Hospital.
The slides were reviewed by pathologists with experience in the diagnosis of melanocytic lesions to identify cases (incipient ulceration) and controls (ulcerated or non-ulcerated).
Incipient ulceration cases were matched in a 1:2 ratio with non-ulcerated and ulcerated controls, respectively. The study analysis was carried out from March to June 2023.
Main results
Clinicopathological factors and clinical outcomes: overall survival (OS), melanoma-specific survival (MSS), and recurrence-free survival (RFS) were compared between cases and controls.
Results
Of 2284 melanoma patients identified, 340 patients (median age [IQR], 69 [24-94] years; 136 [68%] men; median follow-up, 7.2 years) met criteria. The matched cohort consisted of 40 incipiently ulcerated melanoma cases matched 1:2 with 80 non-ulcerated controls and 80 ulcerated controls.
The median (IQR) Breslow thickness differed significantly between cases and controls; 2.8 (1.7-4.1) mm for early cases compared to 1.0 (0.6-2.1) mm and 5.3 (3.5-8.0) mm for melanomas non-ulcerated and ulcerated, respectively.
The median (IQR) tumor mitotic rate was 5.0 (3.0-9.0) per mm2 in the incipiently ulcerated cases compared with 1 (0-3.0) per mm2 in the non-ulcerated controls. and 9 (5.0-14.0) per mm2 in the ulcerated controls.
Based on matched cohorts, patients with nonulcerated tumors had significantly better OS (hazard ratio [HR], 0.49; 95% CI, 0.27-0.88; P = 0.02) and RFS (HR , 0.37; 95% CI, 0.22-0.64). ; P < 0.001) than patients with incipient ulceration.
Recurrence-free survival (RFS) was significantly worse in ulcerated tumors compared with incipiently ulcerated cases (HR, 1.67; 95% CI, 1.07-2.60; P = 0.03).
After adjusting for pathological factors, no statistically significant differences in clinical outcomes were observed between the cases and any of the control groups.
Conclusions and relevance
The findings of this case-control study indicate that incipient ulceration in primary melanoma represents an adverse prognostic feature that pathologists should note in their reports and consider in future guidelines.
