Ulcerated Melanoma: Aspects and Prognostic Impact

Abstract

Ulceration is an important prognostic factor for patients with melanoma and also a predictive marker for the response of adjuvant immunestimulating therapy. A consensual definition and accurate assessment of ulceration is therefore crucial for proper staging and clinical management, but can be difficult even between experienced pathologists. The definition of ulceration is stated differently in the available literature but is generally understood as loss of epidermal matrix. Thinning of the epidermis, also termed consumption of the epidermis (COE), is associated with ulcerated lesions and correlates with enhanced tumor cell proliferation in nonulcerated melanoma. These results suggest that COE may be a proliferative precursor of ulceration, characterized by erosive growth into the epidermal layer (infiltrative type) or expansive growth that may stretch and eventually disrupt the epidermis (attenuative type), which is reflected in the histopathology. We have no means to determine the dynamic changes of human ulcerated melanoma or to determine whether these wounds have re-epithelialization (RE) potential. However, the presence of reactive hyperplasia (REH) and changes indicating RE associates with increased density of neutrophils and may herald resolved or late-stage ulcerations. Combining the extent of ulceration (> or <70% of the total tumor length) and the presence of 68epidermal involvement (COE, REH, and/or RE) stratifies prognosis more accurately and supports the relevance of including these factors in the definition of ulceration and to define ulceration of a primary melanoma as loss of epidermis with evidence of a host response (infiltration of neutrophils or fibrin deposition) and thinning, effacement, or REH of the surrounding epidermis.

Effect of Microdoses of Incisional Antibiotics on the Rate of Surgical Site Infections in Skin Cancer Surgery

“…Both melanoma and nonmelanoma skin cancers are frequently chronically ulcerated and colonized. 25,26 Operative sites are subject to altered perfusion with gravity dependency as well as tension and undermining that can impair immunity during wound healing. 27 Finally, tumor sites may experience fundamentally impaired local immunity, potentiating localized tumorigenesis and subsequent neoplasia.…”

Melanoma stimulates the proteolytic activity of HaCaT keratinocytes

“…Moreover, CAKs exhibited increased motility abilities, which is one of cell features involved in many processes such as wound healing, indicated to be important for ulcers healing, that appear in melanoma patients [ 63 ]. We hypothesize, to the possibility, that increased migration of CAKs have impact on ulceration healing in melanoma.…”

“…Higher proteolytic activity of keratinocytes growing in tumor niche might lead to enhanced migration of cancer cells, as in this way cells create a pathway, which is then used to move through the tissue [62]. Mazurkiewicz et al Cell Communication and Signaling (2022) 20:146 Moreover, CAKs exhibited increased motility abilities, which is one of cell features involved in many processes such as wound healing, indicated to be important for ulcers healing, that appear in melanoma patients [63]. We hypothesize, to the possibility, that increased migration of CAKs have impact on ulceration healing in melanoma.…”

Overcoming Immune Evasion in Melanoma

“…Tumor thickness or Breslow measurement considers the depth of which the melanoma has invaded the skin, since a greater vertical depth is correlated with worse prognosis of melanoma and is associated with greater spread of the disease [56,57]. Furthermore, the extent of ulceration of melanomas gives insight to the spread of the disease, since it frees up the melanoma to grow horizontally or vertically [58][59][60]. Nodal involvement in the TNM criterion evaluates whether the melanoma has spread to the nearby lymph nodes [56].…”