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Image courtesy of Medscape.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | 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 are treated annually 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 (BBC) and squamous cell carcinoma (SCC),[1] accounting for only 1% of such cases[5]; however, it causes the vast majority of skin cancer deaths.[1,5] The American Cancer Society (ACS) estimates that 96,480 invasive melanomas will be diagnosed in 2019, and that 7,230 people will die from melanoma.[5] The exact number of deaths attributable to keratinocyte carcinomas (the term used to collectively describe BCC and SCC, given their shared lineage with epidermal keratinocytes) is not available, as these cancers are not reported to and tracked by registries. While the mortality associated with BCC is exceedingly low, studies have estimated that cutaneous SCC causes from 2,500 to more than 8,000 deaths annually.[6]

The image depicts a malignant melanoma. 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]

Image of a malignant melanoma courtesy of Hon Pak, MD.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Melanoma

Melanoma 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 3 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]

Image of cutaneous metastatic melanoma courtesy of DermNet New Zealand.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | 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 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]

Image courtesy of DermNet New Zealand.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

When detected early, melanoma has a 5-year survival rate of about 98%.[13] However, melanoma has a propensity to spread: If it reaches the lymph nodes, 5-year survival falls to about 62%-63%; with distant metastasis, 5-year survival drops to 17%-18%.[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 an increased risk of developing other cancers, typically a second skin cancer.[9]

The image shows metastatic melanoma from a primary melanoma of the foot.

Image of an ulcerated nodular melanoma courtesy of DermNet New Zealand.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Types of melanoma

Melanomas usually occur on the trunk and extremities, but they may also 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 New Zealand.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Superficial spreading melanoma

Superficial spreading melanoma 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. While most of these melanomas arise de novo, they may appear in association with an existing nevus. The lesion is often identified using the ABCDE criteria discussed in slide 1. 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 papulonodular and raised. One of the main risk factors for metastasis and death is the measured thickness of the melanoma (ie, Breslow depth) at the time the lesion was removed.[18]

Image courtesy of Medscape/Susan M Swetter, MD.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Lentigo maligna and lentigo maligna melanoma

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 may also involve the arms and upper trunk) in the middle-aged and elderly.[15-17] The incidence of this malignancy is increasing.[19,20]

Lentigo maligna may initially resemble a benign pigmented macule (tan, brown, dark brown), which may be mistaken for a "sun spot," (solar lentigo), 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] Patients with recurrence of pigmentation after cosmetic treatment for presumed solar lentigines (eg, laser, cryotherapy, topical bleaching agents) should consider a biopsy to confirm the benign nature and rule out a melanoma.[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, which increases with the Breslow depth. Due to the large size of the lesions and, often, their location on the head and neck, surgery may not always be feasible. Other treatment options include radiation therapy, cryotherapy, and topical immune response modifiers (eg, imiquimod), but these therapies do not offer cure rates as high as those for surgery. Overall, the risk of invasion is low; however, these lesions are notorious for high recurrence rates; thus, close follow-up is warranted.[22]

The image shows lentigo maligna melanoma of the right lower cheek. The centrally located erythematous papule represents an invasive melanoma with surrounding in situ macular lentigo maligna.

Image courtesy of Anthony M Rossi, MD, FAAD.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Acral lentiginous melanoma

Acral lentiginous melanoma is a type 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.[15-17,23] Due to its location, acral lentiginous melanoma is not thought to be caused by sun exposure; also unlike cutaneous malignant melanoma overall, the US incidence appears to have remained stable over time.[23]

Clinically, acral lentiginous melanoma appears as an expanding, asymmetric, discolored patch of skin,[15,17] often with variable pigmentation and less commonly with ulceration and bleeding. The lesions may initially be mistaken for innocuous dark spots or bruises.[23] However, with time these lesions will continue to expand radially and become thicker, with an irregular surface. Affected patients generally have a poor prognosis due to a delayed diagnosis, its aggressive nature, and advanced disease at presentation.[23] The 5- and 10-year survival rates are 80.3% and 67.5%, respectively.[23]

Images of various presentations of nail unit melanoma courtesy of Bristow IR, de Berker DA, Acland KM, Turner RJ, Bowling J. J Foot Ankle Res. 2010;3:25. [Open access.] PMID: 21040565, PMCID: PMC2987777.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | 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.[24] 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.[24,25]

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, or distortion of the overlying nail.[24,25] One way to distinguish subungual melanoma from subungual hemorrhage is that the hemorrhage will move as the nail grows, whereas the melanoma lesions will not,[25] Patients may take serial photographs ("selfie skin examination") of the pigmented nail to monitor change and ensure distal progression of the pigment with nail growth.[26] Diagnosis of melanoma is confirmed with biopsy of the nail matrix and nail bed.

Treatment of nail unit melanoma involves surgical removal—it may also require amputation of the finger or toe[25,27] along with sentinel node biopsy. As with other types of melanoma, the depth of invasion is an important risk factor for metastasis. Delay in diagnosis is common, especially for lesions on the toe, as is the presence of metastatic disease at the time of diagnosis.[25,28] The 5-year survival rate ranges from 16% to 87%.[25]

Image courtesy of Anthony M Rossi, MD, FAAD.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Nodular melanoma

Nodular melanoma is a type 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 type of melanoma.[15,17] The association with sun exposure is not as strong for this subtype of melanoma 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. Given their rapid growth, evolution (or change) can be an important indicator for closer inspection or biopsy. They often present as new spots on the skin, but on rare occasion, nodular melanoma can arise from existing melanocytic nevi.[29]

Nodular melanomas are often invasive when diagnosed and, therefore, portend a worse prognosis. Surgical removal is the mainstay of treatment for the primary lesion.

Image courtesy of Anthony M Rossi, MD, FAAD.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Amelanotic melanoma

Amelanotic melanoma is a type of skin cancer in which the melanocytes do not make melanin.[30] As a result, the lesions may appear in shades of pink, red, white, or the normal color of the background skin. It may occur anywhere on the body, but shows a propensity for chronically sun-exposed sites (eg, head and neck, dorsal hands, anterior lower leg).[31]

Each of the four major melanoma subtypes can occur as amelanotic variants, which have a higher tendency to recur or metastasize than lesions with more typical melanoma characteristics.[30] Moreover, the atypical appearance often leads to a delay in diagnosis when lesions may have had the chance to invade. However, recent studies have shown that when adjusted for Breslow thickness, these lesions have similar mortality outcomes as pigmented melanomas.[31]

Image of squamous cell carcinoma of the ear courtesy of Anthony M Rossi, MD, FAAD.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Keratinocyte Carcinomas

Each year in the United States, approximately 5.4 million cases of keratinocyte carcinoma develop in 3.3 million people.[5] The most common form is basal cell carcinoma, followed by squamous cell carcinoma.[1] An estimated 2,000 to more than 8,500 people die annually from keratinocyte carcinomas (compared with 7,230 deaths from melanoma and 4,420 deaths from other types of skin cancers),[5,32] but the exact numbers are unknown, as these malignancies are not tracked by cancer registries.[5]

Image of a basal cell carcinoma of the nose courtesy of Ramli I, Hassam B. Pan Afr Med J. 2014;19:326. [Open access.] PMID: 25918566, PMCID: PMC4405068.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Basal cell carcinoma

Basal cell carcinoma accounts for nearly 80% of keratinocyte carcinomas.[32] 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.[33] Clinically, basal cell carcinoma appears as a slowly enlarging, non-healing flesh-colored, pink, or pigmented lesion that spontaneously bleeds or ulcerates.[33,34]

Although these tumors are malignant, the rates of metastasis and mortality are each estimated to be less than 1%.[35,36] When metastasis does occur, commonly involved sites include the lymph nodes, bones, lungs, and liver.[33,37] Typically, treatment is surgical, but the therapeutic options depend on the lesion's type, size, number, and site, as well as other patient factors.[33,34] The median survival for individuals with regional metastasis is 87 months, whereas distant metastasis has a shorter survival at 24 months.[37]

Image courtesy of Anthony M Rossi, MD, FAAD.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is derived from epithelial cells responsible for producing keratin.[38,39] Risk factors for this invasive tumor include sun exposure, advanced age, male sex, smoking, thermal burns, human papillomavirus (HPV) 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.[40]

The lesions present as scaling patches or papules with an overlying crust that grow over weeks to months on the head/neck or dorsal extremities.[38,39] Other lesions may appear as shallow to deep ulcers with elevated margins; they may bleed and can be painful. High-risk features include a diameter of 2 cm or larger; more than 2 mm thickness; location on the lip, ear, hands, feet, and genitalia, and within a scar or a chronic wound; presence in elderly or immunosuppressed individuals (eg, transplant recipients); and recurrent lesions.[38,39] Metastatic cSCC may be found in lymph nodes and bones, as well as the lungs, liver, and brain.[39]

Although the prognosis is generally excellent for local disease, a small subset of patients will develop nodal and metastatic disease.[41] Several large studies have shown a mortality greater than 70% for metastatic cSCC.[42] The mainstay of treatment is surgery[39,42]; therapeutic options include surgery with/without radiotherapy, with/without chemotherapy, depending on the location and extent of metastasis.[42]

Image courtesy of Anthony M Rossi, MD, FAAD.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Merkel cell carcinoma

Merkel cell carcinoma (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.[43] Sun exposure, advanced age, and immunosuppression are risk factors.[44] MCC is approximately 25 times more common in fair-skinned than dark-skinned ethnic groups.[45]

The lesion often appears as a rapidly enlarging, painless red or violaceous nodule, most commonly on the head/neck.[44,46] MCC often metastasizes, and may spread rapidly to lymph nodes and bones, as well as the lungs, brain, and other organs.[46,47] Presentation with metastasis to the lymph nodes is not uncommon. Small-volume local disease usually has a better prognosis.[48] Distant disease harbors a very poor prognosis.[44,46] The 5-year survival rate is 51% for local disease, dropping to 14% for distant metastatic spread.[49]

Image courtesy of Anthony M Rossi, MD, FAAD.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Sebaceous carcinoma

Sebaceous carcinoma is a rare and aggressive malignancy originating from sebaceous glands connected to hair follicles of the skin.[50,51] These lesions commonly occur around the eye, stemming from meibomian glands.

The tumors appear as red-yellow, firm nodules on the eyelid margins (most commonly on the upper eyelid) or conjunctiva.[50,51] Many benign conditions mimic sebaceous carcinoma, including chalazion, hordeolum, blepharitis, and conjunctivitis[50,51]—often delaying the diagnosis and potentially increasing mortality.[52] This tumor has a propensity for local recurrence and distant metastasis,[50,53] and it is associated with a poor overall prognosis, with cancer-specific mortality rates from 3% to 30%.[53,54] Sebaceous carcinoma is treated surgically.

Primary cutaneous apocrine carcinomas

Cutaneous tumors of the sweat glands are extremely rare and can be diagnostically challenging, given their relatively nonspecific clinical appearance. Often, they are indolent and slow to develop, however, they may appear as a rapidly growing nodule with aggressive course. They often manifest as a pink plaque or nodule in areas of high apocrine gland density (namely, the axilla, anogenital region, and face) in middle-aged adults.[55] On biopsy, these tumors mimic metastatic adenocarcinoma (often from a breast or gastrointestinal source), and the work-up often entails imaging to rule out a primary visceral source. Surgical excision is standard treatment, though lymph node status is the most important predictor of survival (33 months for patients with positive lymph nodes compared with 55 months for those with node-negative disease).[56] In cases of metastatic disease, multimodal treatment including surgery, radiation, and chemotherapy may be warranted for aggressive tumors.[57]

Images courtesy of Costea R, Vasiliu E, Zarnescu NO, Hasouna M, Neagu S. J Med Life. 2011;4(2):184-8. [Open access.] PMID: 21776304, PMCID: PMC3124261.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Liposarcoma

Liposarcoma is a deep-seated malignancy of fat cells, often appearing as a solitary, slowly enlarging, painless mass.[58] The most commonly affected sites are the lower extremities, groin, and trunk.[58,59]

The tumors generally present as well-circumscribed palpable masses that grow gradually.[48] Patients are often asymptomatic until the mass becomes very large and causes pain and/or functional disruption.[48,49] The tumors can attain a substantial size and weigh multiple pounds to over 100 lb when excised.[60]

Patients with well-differentiated subtypes may live for decades, with a 5-year survival rate of 90%,[61] but local recurrence is a possibility following excision. In contrast, the 5-year survival rate for patients with high-grade liposarcomas ranges from 30% to 75%, depending on the tumor subtype.[61]

The images demonstrate a large, well-differentiated liposarcoma of the right thigh in a middle-aged man. The tumor originated in the popliteal fossa and migrated through the adductor canal (Hunter canal) in the anterolateral muscular space of the thigh.

Image courtesy of Anthony M Rossi, MD, FAAD.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Angiosarcoma

Angiosarcomas are rare, rapidly growing, and extensively infiltrating soft-tissue tumors of endothelial origin that have a poor prognosis.[62-64] Cutaneous angiosarcomas are more often seen in elderly men, frequently occurring on the scalp or upper forehead.

Clinically, cutaneous angiosarcomas may appear as slowly spreading, dusky red patches that may form nodules and ulcerate or bleed.[62,63] 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 its aggressive, multicentric growth, and expansive spread with poorly defined clinical margins; the lesions are often misdiagnosed and have a high local recurrence and metastatic rate.[62-64] Reported 5-year survival rates range from 10% to 30%.[65]

Image courtesy of Anthony M Rossi, MD, FAAD.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Kaposi sarcoma

Kaposi sarcoma is a spindle-cell tumor associated with infection by human herpes virus 8, genetic/hormonal factors, and immunodeficiency.[56] There are four types of Kaposi sarcoma, as follows[67,68]:

  • Epidemic: Related to human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS); the most aggressive and most common subtype of Kaposi sarcoma[67]
  • 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.[66-68] 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.[67]

The tumors have a variable course and may range from a few minor skin lesions to widespread, internal disease.[66-68] Involvement of the digestive tract may cause nausea, vomiting, gastrointestinal bleeding, or abdominal pain, whereas involvement of the lungs may result in coughing, chest pain, hemoptysis, or dyspnea.[67] 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 | January 15, 2019 | Contributor Information

Dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP) 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.[69,70] 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.[69] The trunk is most commonly affected, followed by the proximal extremities; the face and neck are rarely involved. Because of their non-specific clinical appearance as an asymptomatic firm-to-rubbery red/brown plaque or nodule, there is often a delay in diagnosis until the tumor begins to grow rapidly. A skin biopsy is required to confirm the diagnosis. Those DFSPs with fibrosarcomatous change present may be more at risk for recurrence and/or metastasis.

These tumors are locally aggressive and widely invasive, creating a treatment dilemma, given that the primary treatment is surgical excision with wide margins.[69,70] Because of the high local recurrence rate following surgery, close clinical follow-up is warranted. Lymph node and distant metastasis is rare, occurring in less than 5% of cases.[71]

Image courtesy of Anthony M Rossi, MD, FAAD.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Extramammary Paget disease

Extramammary Paget Disease (EMPD) is a rare cancer that occurs typically in the anogenital region.[72] The tumor can arise primarily in the skin, or it may arise from an underlying internal malignancy (most often gastrointestinal or genitourinary).[63] Women and white individuals between ages 50 and 80 years are the most commonly affected.[73]

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.[72] Owing to the heterogeneous appearance of EMPD, multiple topical therapies are often tried because of many clinical mimics before the diagnosis is reached.[73] Newer noninvasive imaging technologies, including reflectance confocal microscopy, may aid in detecting subclinical spread and guiding both surgical and non-surgical management.[74,75]

Surgery is the mainstay of treatment, but topical treatments, radiation therapy, and laser ablation have also been explored. Long-term follow-up is required to exclude recurrence of disease. Disease-specific survival is generally favorable, but poor prognostic factors include older age, perianal disease, dermal invasion, and the presence of distant disease.[76,77]

Image courtesy of Medscape/Robert A Schwartz, MD, MPH.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | 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.[78,79] 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 per 100,000.[80] In the early stages, CTCL is often misdiagnosed as various benign skin conditions, including eczema, contact dermatitis, psoriasis, morphea, and adverse drug reaction[81]—resulting in an average diagnostic delay of 6 years from disease onset.[80]

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), that may thicken, ulcerate, or form large tumors.[66,69] 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.[78,81]

With few exceptions, CTCL remains incurable and treatment is largely palliative.[78,80] 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% to 27%, with a median survival of approximately 3 years.[82,83]

Image courtesy of Anthony M Rossi, MD, FAAD.

Deadly Skin Cancers

Brian P Hibler, MD; Anthony M Rossi, MD, FAAD | January 15, 2019 | Contributor Information

Skin cancers in immunosuppressed individuals

Immunosuppression, either pharmacologic or physiologic, appears to increase the risk of skin cancer.[84,85] For example, solid organ transplant recipients have an estimated 65- to 250-fold increased risk of developing cutaneous squamous cell carcinoma (cSCC) compared with the general population and a 6- to 10-fold increased risk for basal cell carcinoma; the risk of melanoma and Kaposi sarcoma is also raised.[86,87] Other at-risk groups include individuals with HIV infection and those with hematologic malignancies. Skin cancers in these groups, especially cSCC, may have uncommon clinical features and are particularly aggressive, with high rates of recurrence and metastasis.

Preventive measures, regular skin examination, early detection, and appropriate treatment are critical to minimize morbidity and mortality. Nicotinamide 500 mg twice daily may provide safe and effective chemo-prevention of non-melanoma skin cancer in high-risk individuals.[89] Treatment with systemic retinoids, topical agents, and photodynamic therapy may be used where 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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Mole or Melanoma? Test Yourself With These Suspicious Lesions

Melanoma accounts for less than 5% of skin cancer cases but most skin cancer–related deaths. Early detection is the best means of reducing mortality. Can you correctly diagnose these skin lesions?Slideshows, July 2017
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Malignant Melanoma

Malignant melanoma is a neoplasm of melanocytes or a neoplasm of the cells that develop from melanocytes. Although it was once considered uncommon, the annual incidence has increased dramatically over the past few decades.Diseases/Conditions, June 2018
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References