Primary melanomas with incipient ulceration may be “more biologically aggressive” than nonulcerated melanomas despite being grouped together for staging – and should not be overlooked by pathologists, Australian researchers warn.
Their study found that tumours with incipient ulceration were significantly thicker, more mitotically active and significantly more likely to have lymphovascular invasion, positive sentinel nodes and satellite lesions than nonulcerated controls.
Writing in JAMA Dermatology [link here], the researchers, which included Melanoma Institute Australia pathologists and surgical oncologists, said their findings challenged the American Joint Committee on Cancer’s classification of incipiently ulcerated cases as “lower-risk” under the current staging system.
The retrospective case-control study consisted of 340 patients (median age 69, 68% male) with resected primary cutaneous melanomas diagnosed between 2005 and 2015 and identified using the Melanoma Institute Australia research database.
Slides were available for review by pathologists experienced in the diagnosis of melanocytic lesions from the Royal Prince Alfred Hospital, Sydney.
Incipient ulceration was defined as severe thinning of the epidermis (with ≤3 layers of nucleated keratinocytes and/or residual stratum corneum) directly overlying a melanoma tumor, with evidence of a host response (serum/fibrin and neutrophils).
The cohort consisted of 40 cases of incipiently ulcerated melanoma matched with 80 nonulcerated controls and 80 ulcerated controls.
Findings suggested that the median Breslow thickness differed significantly between the matched cases and controls; 2.8mm for incipient cases compared with 1.0mm and 5.3mm for nonulcerated and ulcerated melanomas, respectively.
Almost a quarter of melanomas (23.7%) in acral sites showed incipient ulceration compared with 10.3% of nonacral melanomas, noted the researchers.
The median tumor mitotic rate was 5.0 per mm² in incipiently ulcerated cases versus 1 and 9 per mm² in nonulcerated and ulcerated controls, respectively.
Patients with nonulcerated tumours had significantly better overall survival (HR 0.49) and recurrence-free survival (HR 0.37) than patients with incipient ulceration. Recurrence-free survival was significantly worse in ulcerated tumours compared with incipiently ulcerated cases (HR 1.67).
There was no significant difference in melanoma-specific survival.
Median overall survival for patients with incipient ulceration was 7.9 years, compared with 3.7 years for those with ulcerated tumours and 10.4 years for those with nonulcerated tumours.
The authors observed that incipient ulceration was often present at the edges of true ulceration, which suggested that these features fell along a continuum.
“In some cases, incipient ulceration was seen in tissue slices adjacent to the slice(s) with true ulceration, raising the possibility that in a subset of cases of incipient ulceration, true ulceration may exist nearby, simply unprofiled in the sections,” they said.
“Taking these findings and observations together, it seems likely that for many tumours, the mitotic rate, size, thickness, and presence of ulceration are all interrelated parameters: the most biologically aggressive cutaneous melanomas show rapid proliferation, resulting in larger, thicker tumours that initially cause attenuation or consumption of the overlying epidermis, possibly followed by a phase of incipient ulceration before becoming truly ulcerated.”
The researchers concluded that moving forward, pathologists should comment on the presence of incipient ulceration in their pathology reports of primary melanomas, so that related data on this feature could continue to be collected.