Desmoplastic melanoma (DM) is an uncommon subtype of melanoma, with distinct clinical and histopathological features, accounting for less than 4% of all cutaneous melanomas.

DM most commonly affects sun-exposed areas, such as the head and neck. The trunk and extremities may also be the primary site, and most cases in women arise on the lower extremities. Rarely, non-sun-exposed areas such as acral surfaces and mucosal sites can be affected.

DM is most common in older White men. The male-to-female occurrence ratio has been reported near 2:1. Younger populations are not excluded. Rare cases of pediatric DM have been found in association with xeroderma pigmentosum and other DNA repair disorders. DM can affect all races / ethnicities, although it is rarer in darker skin types.

Clinically, DM presents as an indurated, firm, amelanotic or melanotic papule, plaque, or nodule. It may have a scar-like appearance. Around 70% of DMs are amelanotic. Ulceration may occur in long-standing lesions. DM commonly arises de novo or in association with lentigo maligna. It is less frequently associated with acral lentiginous melanoma or preexisting nevi.

DM is defined histopathologically by invasive, often amelanotic, spindle cells embedded in a dense collagen stroma. Two histological subtypes are recognized: pure DM and mixed DM. Mixed DM resembles conventional melanoma, with a greater frequency of nodal spread and a poorer prognosis than pure DM. Local recurrence is common in both subtypes, partly due to the characteristic perineural invasion from tumors exhibiting neurotropism. The progression of DM is typically slow and localized, often limited to the reticular dermis at diagnosis. Mixed DM, however, tends to exhibit greater potential for lymph node and distant metastases.

Pathogenetically, chronic ultraviolet (UV) exposure induces a high mutation burden in genes such as TP53, NF1, and NFKBIE. BRAF V600E mutations are typically limited to mixed DM, which may contribute to differences in therapeutic responsiveness.