In addition, it has long been speculated that melanomas express neoantigens that should be subject to recognition by the immune system. It follows that for melanoma to develop, tumor cells must acquire the ability to either suppress or evade the host immune response. The importance of immune evasion has been proven by the response of many advanced melanomas to immune checkpoint inhibitors, agents that unleash muzzled melanoma-specific T cells, allowing them to attack the tumor (described later).
MORPHOLOGYUnlikebenignnevi,melanomasoftenexhibitstriking variations in pigmentation, includingshadesofblack,brown,red,darkblue,andgray(
Fig.24.23A ).Theborders are irregular andoften“notched.”Microscopically,malignantcellsgrowaspoorlyformednestsorasindividualcellsatalllevelsoftheepidermis(pagetoidspread)andinexpansiledermalnodules;theseconstitutetheradialandverticalgrowthphases,respectively(
Fig.24.23B-C ).Ofnote,superficialspreadingmelanomasareoftenassociatedwithabrisklymphocyticinfiltrate(
Fig.24.23B ),afeaturethatmayreflectahostresponsetotumor-specificantigens.Increasing thickness strongly correlates with worse biologic behavior of melanomas (termed Breslow thickness). Byrecordingandusingtheseandothervariablesinaggregate,accurateprognosticationispossible.
Individualmelanomacellsusuallyareconsiderablylargerthannevuscells.Theyhavelargenucleiwithirregularcontours,chromatinthatischaracteristicallyclumpedattheperipheryofthenuclearmembrane,andprominent“cherryred”eosinophilicnucleoli(
Fig.24.23D ).Immunohistochemicalstainscanbehelpfulinidentifyingmetastaticdeposits(
Fig.24.23D , inset).
Although most of these lesions arise in the skin, they also may occur in the oral and anogenital mucosal surfaces, the esophagus, the meninges, and the eye. The following discussion applies to cutaneous melanomas.
Melanoma of the skin usually is asymptomatic, although pruritus may be an early manifestation. The most important clinical sign is a change in the color or size of a pigmented lesion. The main clinical warning signs are as follows: 1.
Rapid enlargement of a preexisting nevus 2.
3.
Development of a new pigmented lesion during adult life 4.
Irregularity of the borders of a pigmented lesion 5.
Variegation of color within a pigmented lesion
These principles are expressed in the so-called “ABCs” of melanoma: asymmetry, border, color, diameter, and evolution (change of an existing nevus). It is vitally important to recognize melanomas and intervene as rapidly as possible. The vast majority of superficial lesions are curable surgically, while metastatic melanoma has a very poor prognosis.
The probability of metastasis is predicted by measuring the depth of invasion in millimeters of the vertical growth phase nodule from the top of the granular cell layer of the overlying epidermis (Breslow thickness). Metastasis risk also is increased in tumors with a high mitotic rate and in those that fail to induce a local immune response. When metastases occur, they involve not only regional lymph nodes but also liver, lungs, brain, and virtually any other site that can be seeded hematogenously. Sentinel lymph node biopsy (of the first draining node[s] of a primary melanoma) at the time of surgery provides additional information on biologic aggressiveness.