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Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022
| Contributor Information
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Cutaneous squamous cell carcinoma (cSCC) is shown. Image courtesy of Anthony M Rossi, MD, FAAD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Skin cancer is the most common form of cancer in the United States.[1-4] An estimated 8,500 people are diagnosed with skin cancer every day, and nearly 5 million people annually are treated for it.[2,4] The incidence and associated healthcare expenditures continue to rise, making skin cancer a major public health concern.[2,4]
Although many skin cancers are highly curable if detected early and appropriately treated, certain types are particularly aggressive and have a propensity for invasion and metastasis. For example, melanoma is the third most common type of skin cancer, after basal cell carcinoma (BCC) and SCC,[1,6] accounting for only 1% of such cases[5]; however, it causes the vast majority of skin cancer deaths.[1,5] The American Cancer Society estimated that 99,780 invasive melanomas would be diagnosed in 2022 and that 7,650 people would die from melanoma.[5]
Image courtesy of Medscape | Hon Pak, MD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Melanoma
Melanoma (shown) originates in melanocytes.[7] These cells produce melanin, the pigment that gives skin its color and protects the deeper skin layers from the sun.
The US incidence of melanoma has been rising for the past three decades.[5] This disease is deadly, second only to adult leukemia with respect to the years of potential life lost in young adults, and it is responsible for a disproportionately high number of deaths in young and middle-aged adults.[8] In the above image, note the presence of asymmetry, border irregularity, color variation, a large diameter (>6 mm), and an elevated (evolving) appearance—these "ABCDEs" outline the characteristic clinical signs of melanoma.[5]
Ulcerated melanoma on the ear, with in-transit metastases is shown. Image courtesy of Brett Sloan, MD, FAAD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Although melanoma can occur anywhere on the skin, the most commonly affected sites are the chest and back in men and the legs in women.[9] Most melanomas are deeply pigmented, being brown or black, but variegated colors may occur, with lesions appearing pink, red, white, or tan (amelanotic melanoma).[9]
An estimated 86% of cases of melanoma are attributed to excessive ultraviolet radiation.[10] Regular daily use of sunscreen may reduce the risk of developing melanoma by about 50%.[11] Other risk factors for the development of melanoma include the presence of atypical and/or multiple nevi, fair skin, freckling, light-colored hair, personal or family history of melanoma or other skin cancers, and a weakened immune system.[5,9,12]
When detected early, melanoma has a 5-year relative survival of about 98.7%.[13] However, melanoma has a propensity to spread; if it reaches the lymph nodes, 5-year relative survival falls to less than 65%. With distant metastasis, 5-year relative survival drops to 24.8%.[5,13]
Surgery is the mainstay of therapy, but other treatment options include immunotherapy, targeted therapy, chemotherapy, and radiation therapy.[5,12] Regular follow-up after treatment is important to evaluate for recurrence. Moreover, individuals with a personal history of melanoma are at increased risk of developing other cancers, typically a second skin cancer.[9]
Images from Mandel Y, Laufer S, Belkin M, Rubinsky B, Pe'er J, Frenkel S. PLoS One. 2013;8(9):e71789. PMID: 24039721; PMCID: PMC3764134. [Creative Commons Attribution License.]
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
The images shown depict uveal melanomas. The left image is a B-scan eye ultrasound revealing a choroidal tumor with shallow-rimming retinal detachment. The right image shows a bisected enucleated eye. The long arrow points to the tumor; the short arrow points to the optic nerve.
Types of melanoma
Melanomas usually occur on the trunk and extremities, but they also may arise elsewhere, including the eye (uveal melanoma) and the lining of the mouth, vagina, and gut (mucosal melanoma).
On the basis of their growth pattern, cutaneous melanomas are divided into the following four basic categories[14-17]:
Superficial spreading (70%) - Begins in situ (confined to the epidermis)
Lentigo maligna (10%) - Begins in situ
Acral lentiginous (5%) - Begins in situ
Nodular (10-15%) - Invasive from the beginning
Image courtesy of DermNet NZ.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Superficial spreading melanoma
Superficial spreading melanoma (shown) is the most common subtype of melanoma.[14-17] In this form, malignant cells tend to spread superficially in the epidermis over a prolonged period (radial growth phase).[14-17] Clinically, it appears as a slowly enlarging, flat area of discolored skin. The most common site for men is the back, and for women, the legs.
An unknown proportion of these tumors become invasive—and potentially life threatening. During the vertical growth phase, these lesions may become raised. One of the main risk factors for metastasis and death is the measured thickness of the melanoma (ie, Breslow depth) at the time of the lesion's removal.[18]
Image courtesy of Medscape | Susan M Swetter, MD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Lentigo maligna and lentigo maligna melanoma
In the above image of the right lower cheek, the centrally located erythematous papule represents an invasive melanoma, with in situ macular lentigo maligna surrounding it.
Lentigo maligna is a form of in situ melanoma that correlates with sun exposure and photodamage. It occurs on chronically sun-damaged skin (typically the head and neck, but it also may involve the arms and upper trunk) in middle-aged and elderly individuals.[15-17] The incidence of this malignancy is increasing.[19,20]
Lentigo maligna initially may resemble a benign pigmented macule (tan, brown, dark brown), but it slowly grows to form large brown, flat or slightly raised patches often characterized by an irregular shape, variable pigment coloration, and a smooth surface that may thicken when the tumor becomes invasive.[15-17,21]
In its invasive counterpart, lentigo maligna melanoma, malignant cells have invaded the dermis and deeper layers of the skin[22]; this form has the potential for metastasis.
Image courtesy of Anthony M Rossi, MD, FAAD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Acral lentiginous melanoma
Acral lentiginous melanoma is a subtype of melanoma that occurs on the palms and soles (shown) and under the nails.[15-17] Although it is equally rare in light- and dark-skinned individuals, its proportion among all melanoma subtypes is significantly higher in people of color, particularly Asian and Black individuals.[15-17,22] Owing to its locations, acral lentiginous melanoma is not thought to be caused by sun exposure.
Clinically, acral lentiginous melanoma appears as an expanding, asymmetrical, discolored patch of skin,[15,17] often with variable pigmentation and, less commonly, with ulceration and bleeding. Over time, these lesions continue to expand radially and become thicker, with an irregular surface. Affected patients generally have a poor prognosis; the 5- and 10-year survival rates are 80.3% and 67.5%, respectively.[22]
Various presentations of nail unit melanoma are shown. Images from Bristow IR et al. J Foot Ankle Res. 2010;3:25. PMID: 21040565; PMCID: PMC2987777. [CC Attribution 2.0 Generic License (CC by 2.0).]
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Nail unit melanoma/subungual melanoma
Melanoma of the nail unit (subungual melanoma) is a rare subtype of acral lentiginous melanoma,[17] accounting for about 1% of all cases of melanoma.[23] The lesion often initially presents as a pigmented band visible beneath the nail plate (melanonychia). However, a relatively large number of lesions (15-65%) are amelanotic, thereby obscuring detection and diagnosis.[23,24]
Concerning features include widening of the band (especially at the proximal end near the cuticle), variegated colors, involvement of the proximal nail fold (ie, Hutchinson sign), formation of a nodule, bleeding, and distortion of the overlying nail.[23-25] Diagnosis of melanoma is confirmed with biopsy of the nail matrix.
Image courtesy of Anthony M Rossi, MD, FAAD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Nodular melanoma
Nodular melanoma (shown) is a subtype of invasive melanoma in which the malignant cells proliferate downward (vertical growth).[14,16,17] Nodular melanoma has a more rapid growth rate than other forms of melanoma and is the most aggressive melanoma subtype.[15,17] The association with sun exposure is not as strong for this subtype as it is for the superficial spreading and lentigo maligna variants.
Clinically, nodular melanoma appears as a rapidly enlarging, blue/black, dome-shaped lesion, typically on the head, neck, and trunk of middle-aged to elderly individuals.[15-17] Some tumors may lack the traditional ABCD criteria or may lack pigment, appearing pink/red in color. They often present as new spots on the skin, but on rare occasions, nodular melanoma can arise from existing melanocytic nevi.[23]
Image courtesy of Anthony M Rossi, MD, FAAD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Amelanotic melanoma
Amelanotic melanoma (shown) is a type of skin cancer in which the melanocytes do not make melanin.[27] As a result, the lesions may appear in shades of pink, red, or white, or they may have the normal color of the background skin. This melanoma may occur anywhere on the body but shows a propensity for chronically sun-exposed sites (eg, head and neck, dorsal hands, anterior lower leg).[28]
Each of the four major melanoma subtypes can occur as amelanotic variants, which have a higher tendency to recur or metastasize than do lesions with more typical melanoma characteristics.[27] Studies have shown that when adjusted for Breslow thickness, these lesions have mortality outcomes similar to those for pigmented melanomas.[28]
Image courtesy of Anthony M Rossi, MD, FAAD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Keratinocyte Carcinomas
An SCC of the ear is shown above.
Each year in the United States, approximately 5.4 million cases of keratinocyte carcinoma develop in 3.3 million people.[5,6,29] The most common form is BCC, followed by SCC.[1] It is estimated that between 2,500 and more than 8,000 deaths result from cSCC annually (compared with 7,230 deaths from melanoma and 4,420 deaths from other types of skin cancers),[5,29] but the exact numbers are unknown since keratinocyte malignancies are not tracked by cancer registries.[5]
BCC of the nose is shown. Image from Ramli I, Hassam B. Pan Afr Med J. 2014;19:326. PMID: 25918566; PMCID: PMC4405068. [CC Attribution International 4.0 License (CC by 4.0).]
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Basal cell carcinoma
BCC accounts for nearly 80% of keratinocyte carcinomas.[29] These epithelial tumors generally have an excellent prognosis when detected early; however, if the lesions are neglected or allowed to progress, they can be locally destructive and invasive.[30] Clinically, BCC appears as a slowly enlarging, nonhealing, flesh-colored, pink, or pigmented lesion that spontaneously bleeds or ulcerates.[30,31]
Although these tumors are malignant, the rates of metastasis and mortality are each estimated to be less than 1%.[32,33] When metastasis does occur, commonly involved sites include the lymph nodes, bones, lungs, and liver.[30,34] Typically, treatment is surgical, but the therapeutic options depend on the lesion type, size, number, and site, as well as other patient factors.[30,31] The median survival for individuals with regional metastasis is 87 months, whereas distant metastasis is associated with shorter survival, at 24 months.[34]
SCC is shown. Image from the National Cancer Institute. [Public domain.]
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Squamous cell carcinoma
cSCC is derived from epithelial cells responsible for producing keratin.[35,36] Risk factors for this invasive tumor include sun exposure, advanced age, male sex, smoking, thermal burns, human papillomavirus infection, immunosuppression, and a previous history of skin cancers. Solid organ transplant recipients are estimated to be at 100-fold higher risk of developing cSCC compared with the general population.[37]
The lesions typically present as scaly patches or papules with an overlying crust that grow over weeks to months on the head/neck or dorsal extremities.[35,36] Other lesions may appear as shallow-to-deep ulcers with elevated margins; they may bleed and can be painful. Metastatic cSCC may be found in lymph nodes and bones, as well as in the lungs, liver, and brain.[36]
Although the prognosis is generally excellent for local disease, a small subset of patients develop nodal and metastatic disease.[38] Several large studies have shown a greater than 70% mortality for metastatic cSCC.[39] The mainstay of treatment is surgery,[36,39] and therapeutic options include surgery with/without radiotherapy, with/without chemotherapy, depending on the location and extent of metastasis.[39]
Image courtesy of Brett Sloan, MD, FAAD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Merkel Cell Carcinoma
The above image shows a leg with multiple Merkel cell carcinoma (MCC) lesions.
MCC is a rare, aggressive primary cutaneous neuroendocrine tumor that is believed to arise from Merkel cells in or near the epidermal basal layer. An estimated 2,500 new cases of MCC are diagnosed annually in the United States, and this number is expected to continue to rise.[40] Sun exposure, advanced age, and immunosuppression are risk factors.[41] MCC is approximately 25 times more common in fair-skinned than dark-skinned ethnic groups.[42]
The lesion often appears as a rapidly enlarging, painless, red or violaceous nodule, most commonly on the head/neck.[41,43] MCC often metastasizes and may spread rapidly to lymph nodes and bones, as well as to the lungs, the brain, and other organs.[43,44] Five-year survival is 51% for local disease, dropping to 14% for distant metastatic spread.[45]
Image courtesy of Anthony M Rossi, MD, FAAD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Angiosarcoma
Angiosarcomas are rare, rapidly growing, extensively infiltrating soft-tissue tumors of endothelial origin that have a poor prognosis.[46-48] Cutaneous angiosarcomas are more often seen in elderly men, frequently occurring on the scalp or upper forehead (shown).
Clinically, cutaneous angiosarcomas may appear as slowly spreading, dusky red patches that may form nodules and ulcerate or bleed.[46,47] Treatment depends on the size, location, and extent of the tumor and may involve surgery with/without radiation and/or chemotherapy. However, management is complicated by angiosarcoma's aggressive, multicentric growth and expansive spread with poorly defined clinical margins; the lesions are often misdiagnosed and have high local recurrence and metastatic rates.[46-48] Reported 5-year survival rates range from 10-30%.[49]
Image courtesy of Anthony M Rossi, MD, FAAD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Kaposi Sarcoma
Kaposi sarcoma (shown) is a spindle-cell tumor associated with infection by human herpes virus 8, genetic/hormonal factors, and immunodeficiency.[50] The four types of Kaposi sarcoma are as follows[51,52]:
Epidemic: Related to HIV/AIDS; the most aggressive type of Kaposi sarcoma[51]
Endemic: African
Iatrogenic: Immune suppression–related
Classic/sporadic
The lesions typically involve the skin and oral mucosa, but the lymph nodes and internal organs may also be affected.[50-52] Clinically, Kaposi sarcoma appears as painless red-to-purple patches or papules/nodules on the skin. These cutaneous lesions may be cosmetically disfiguring and generate psychological distress.[51]
The tumors have a variable course and a range of manifestations, from a few minor skin lesions to widespread internal disease.[50-52] Pulmonary involvement with uncontrolled pulmonary hemorrhage is the most common cause of death. Treatment depends on the type and extent of Kaposi sarcoma.
Image courtesy of Anthony M Rossi, MD, FAAD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Dermatofibrosarcoma Protuberans
Dermatofibrosarcoma protuberans (DFSP; shown) is a very rare soft-tissue tumor (<5 cases per 1 million people annually) with a propensity for local recurrence; it is associated with substantial morbidity.[53,54] The tumor arises from the dermis and may develop fingerlike projections that invade deep into muscle and other tissues.
Clinically, DFSP has a very innocuous appearance, often presenting as a slow-growing, painless, violaceous nodule that may be fixed to deeper structures beneath the skin.[53] The trunk is most commonly affected, followed by the proximal extremities; the face and neck are rarely involved. A skin biopsy is required to confirm the diagnosis.
These tumors are locally aggressive and widely invasive, and the primary treatment is surgical excision with wide margins.[53,54] Lymph node and distant metastasis is rare, occurring in less than 5% of cases.[55]
Image courtesy of Anthony M Rossi, MD, FAAD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Extramammary Paget Disease
Extramammary Paget disease (shown) is a rare cancer that occurs typically in the anogenital region.[56] The tumor can develop primarily in the skin, or it may arise from an underlying internal malignancy (most often gastrointestinal or genitourinary). Women and White individuals between ages 50 and 80 years are the most commonly affected.[57]
Patients often report mild-to-intense pruritus and pain in the affected areas; clinically, the lesions appear as an eczematous, erythematous, raised area of skin with scaling or ulceration.[56]
Surgery is the mainstay of treatment, but topical treatments, radiation therapy, and laser ablation have also been explored. Disease-specific survival is generally favorable, but poor prognostic factors include older age, perianal disease, dermal invasion, and the presence of distant disease.[58,59]
Image courtesy of Medscape | Robert A Schwartz, MD, MPH.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Cutaneous T-Cell Lymphoma
Primary cutaneous lymphomas represent a heterogeneous group of non-Hodgkin lymphomas that are characterized by a cutaneous infiltration of monoclonal lymphocytes.[60,61] The most common form is cutaneous T-cell lymphoma (CTCL), which typically affects adults (median age, 55-60 years) and has an estimated annual incidence of 0.5 cases per 100,000 population.[62]
Clinically, CTCL lesions may appear as red-to-brown patches of skin, primarily on sun-protected areas that a bathing suit would cover (eg, chest, buttocks, lower trunk). These patches may thicken, ulcerate, or form large tumors. When CTCL affects the entire body, it is known as Sézary syndrome. Patients may develop red, scaly skin over large portions of the body (erythroderma), and there is lymph node and bloodstream involvement.[60,63]
With few exceptions, CTCL remains incurable, and treatment is largely palliative.[60,62] Early-stage CTCL often runs a very indolent course, with little to no impact on overall survival; however, individuals with Sézary syndrome have a 5-year survival of 12.5-27%, with a median survival period of approximately 3 years.[64,65]
Image courtesy of Anthony M Rossi, MD, FAAD.
Deadly Skin Cancers
Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | April 22, 2022 | Contributor Information
Skin Cancers in Immunosuppressed Individuals
Immunosuppression, either pharmacologic or physiologic, increases the risk for skin cancer.[66,67] For example, solid organ transplant recipients have an estimated 65- to 250-fold increased risk of developing cSCC compared with the general population, and a 6- to 10-fold increased risk for BCC; the risk for melanoma and Kaposi sarcoma is also raised.[68,69] Other at-risk groups include individuals with HIV infection and those with hematologic malignancies.
Preventive measures, regular skin examination, early detection, and appropriate treatment are critical to minimizing morbidity and mortality. Nicotinamide 500 mg twice daily may provide safe and effective chemoprevention for nonmelanoma skin cancer in high-risk individuals.[70] Treatment with systemic retinoids, topical agents, and photodynamic therapy may be used if there is an extensive area of actinic damage and epidermal dysplasia (ie, field cancerization). However, aggressive surgical therapy is warranted for more high-risk tumors.
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Contributor Information
Authors
Brian P Hibler, MD
Dermatologist
Schweiger Dermatology - Penthouse
New York, New York, United States
Disclosure: Brian P Hibler, MD, has disclosed no relevant financial relationships.
Anthony M Rossi, MD, FAAD
Assistant Attending
Dermatologic Surgeon
Memorial Sloan Kettering Cancer Center; Assistant Professor of Dermatology; Assistant Attending New York Presbyterian Hospital at Weill Cornell Medical College
New York, New York, United States
Disclosure: Anthony M Rossi, MD, FAAD, has disclosed financial relationships with the following:
Canfield Scientific; Allergan PLC; Cutera, Inc., Maviq GmbH, Merz Pharmaceuticals GmbH
Reviewer
Brett Sloan, MD, FAAD
Professor of Dermatology
University of Connecticut School of Medicine;
Residency Site Director
Connecticut Veterans Affairs Healthcare System;
Assistant Clinical Professor
Yale University School of Medicine;
Editor-in-Chief
Journal of the American Academy of Dermatology Case Reports
Disclosure: Brett Sloan, MD, FAAD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Journal of the American Academy of Dermatology.
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