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Jaffe Leland: Welcome to part II of dermatology. The learning objectives of this lecture include review of common skin neoplasms including benign pigmented lesions, squamous and basal cell carcinomas and we will end with the discussion on melanomas. Let's begin this lecture by discussing pigmented skin lesions. We will begin our discussion of pigmented skin lesions by discussing nevomelanocytic nevus aka moles. This can be broken up into three different categories based on the level of tissue depth within the epidermal or dermal tissues. The junctional nevomelanocytic nevus are the most superficial nevi and are located on the epidermal side of the dermoepidermal junction. These never exceed 1 centimeter in diameter and are macular in presentation and that they are flat. They are also uniform in color either tan, brown, black in color and round with smooth regular borders. As nevi extend deeper into the tissue layers involving the papillary dermis, they start to elevate above the skin surface and develop into a papular or small nodular presentation, often dark brown or black in presentation in dome shaped. Finally, dermal melanocytic nevus are the deeper nevi located within the deeper layers of the dermis. This often presents as a sharply defined papular or nodular presentation and the diameter also is often less than 1 cm in diameter. This picture on the right hand side of this slide presents the three different types of nevi with the different levels of tissue distribution within the upper dermal and dermal tissue layers. The clinical photo on the left hand side of the screen demonstrates a small circular brown macule at the fourth interdigital space of the patient's hand utilizing a hand-held dermascope.

[02:04]

And under dermoscopic evaluation, we can parallel furrows that are homogenous in pattern, which are common on palmoplantar lesions and this would designate this as a benign junctional nevomelanocytic nevus. Acquired nevomelanocytic nevi are also known as common moles. These are often small less than 1 cm in diameter. They are usually well-circumscribed, homogenous in color and can present as macular papular or nodular presentation based on the level of tissue depth within the epidermal or dermal tissue layers. The onset is typically in childhood during the first three decades of life and is common for most adults to have about 20 normal nevomelanocytic nevi. The risk of melanoma during the patient's lifetime is related to the number of normal nevomelanocytic nevi as well as atypical nevomelanocytic nevi. If a patient has greater than 5 atypical nevi and greater than 50 nevomelanocytic nevi, the patient is at a greater risk during their lifetime of developing a melanoma. Atypical melanocytic nevi can also be known as a dysplastic nevus or Clark's nevus. This is a proliferation of atypical melanocytes that is clinically distinctive from the common nevi that were presented earlier. These are generally larger, greater than 1 cm size in diameter. There is often color variation within the lesion. The same lesion may have dark brown, light brown, tan, pink colors within the same lesion. There is asymmetry in the lesion itself with irregular or notched borders. The patients with the atypical nevi have a greater risk of developing a superficial spreading melanoma or another type of melanoma during the course of their lifetime. As stated on the previous slide if the patient who has greater than five atypical melanocytic nevi, the risk increases to develop a melanoma during their lifetime.

[04:07]

A blue nevus is a type of acquired benign nevi that presents when melanocytes aggregate within the dermal tissue layer. Melanocytes typically present within the basal layer of the epidermis. So this is an atypical distribution of melanocytes within the dermal tissue layer. The onset of these lesions is during childhood to late adolescents. If the patient develops this clinical presentation later on in life, the probability of a malignancy increases. The pathogenesis of this condition is an ectopic accumulation of melanin within the dermal tissue layers and what happens is the brown pigment absorbs the longer wavelength of light and scatters the blue light. This is called the Tyndall effect and this is why these lesions appear blue in color. Treatment, there is no treatment necessary if they are less than 10 mm in size and stable and don't progress during that patient's lifetime. If there is an enlargement within these lesions or sudden change in appearance, a biopsy is indicated and treatment may be necessary. The next benign pigmented skin lesion that will be discussed is the seborrheic keratosis, which is also known as a basal cell papillomatosis. This is a very common benign cutaneous tumor that only involves the epidermis with no malignant potential transformation within this lesion. The onset is typically in a middle-to-late adulthood on sun exposed surfaces and it's uncommon to see these lesions appear before the age of 30. This lesion has a classic, waxy, stuck-on appearance and can involve all skin surfaces except the palms and soles. This is the most common source of melanoma misdiagnosis and if a biopsy is performed, the histological hallmark is a horn cyst where there is a continuous communication with the external surface.

[06:00]

The picture on the bottom right hand side of this slide demonstrates this histological appearance. Keratoacanthomas are the next lesions that will be discussed. These are benign epithelial tumors that closely resemble a squamous cell carcinoma. These appear as a smooth dome-shaped papule with a center keratin filled crater. There is a rapid growth rate with these lesions as compared to squamous cell carcinomas that often grow much more slowly. There is an unknown etiology and these commonly present in patents greater than 65 years of age in sun exposed areas such as the face. If it's difficult to distinguish these from a squamous cell carcinoma, it is indicated to perform a biopsy. These may present in patients with a previous HPV infection, chronic exposure to UV radiation or exposure to chemical carcinogens. These often will spontaneously resolve within two to six months; however, if they cannot be distinguished from a squamous cell carcinoma, surgical excision is recommended. Moving along the next benign lesion that will be discussed is the epidermoid cyst, which is a dermal nodule that is often mobile in presentation. This appears as a flesh-colored, superficial papule or nodule. There is enclosure of the epidermis within the dermis tissue and epidermis is still proliferating keratin and keratin gets encapsulated within a cyst. If this lesion is popped, the cheesy contents within the cyst has a classic rancid smell. The locations of these cysts are common on the scalp, ears, back or chest. Treatment involves excision of the cyst deep to the level of the subcutaneous tissue to minimize the chance of recurrence of this lesion.

[08:00]

The next benign lesion I will discuss is the dermatofibroma. This is a very common skin lesion that typically presents in the lower extremity or trunk. It commonly presents on the anterior surface of the lower extremity. This may have the clinical appearance that might look similar to a melanoma especially when there is darker pigmentation. Biopsy would be indicated this time if melanoma was a differential diagnosis. This is a common skin lesion seen in adults with a higher female predilection. There is an unknown etiology; however, it has been suggested that it might occur following an arthropod bite such as tic, mosquito, lice or fleas. It also might be a fibrous reaction to trauma or it might be secondary to a viral skin infection. The classic clinical maneuver to determine if a skin lesion is a dermatofibroma is a squeeze test, which will cause a retraction of the central aspect of the lesion, sometimes termed the dimple sign. The final benign skin lesion included in this lecture is cutaneous horn, which is a hard conical projection of keratin, often present on sun-exposed areas of the body including the face, ears or hands. These are noncancerous lesions; however, there may be a squamous cell in situ lesion or a squamous cell carcinoma present at the base of these lesions. They might arise from a previous seborrheic keratosis, a verruca infection of the skin or keratoacanthoma. The cutaneous horn may vary in size from a few millimeters to few centimeters and can also vary in color as well as shape. As stated on the previous slide, it is indicated to excise these lesions from the skin and perform a biopsy as squamous cell carcinoma in situ or invasive squamous cell carcinoma may be present at the base of these lesions, at which case it will be indicated to perform either cryosurgery or surgical excision to remove the lesion in total. Next, we will transition to the precancerous as well as the epidermal skin cancer including the squamous cell carcinoma, the basal cell carcinoma as well as melanoma.

[10:08]

The first two epidermal skin cancers that we will discuss are the basal cell carcinoma as well as squamous cell carcinoma. These two different types of carcinoma vary in their cell of origin as well as their level of invasiveness and risk of metastasis as a squamous cell carcinoma has a much greater risk of distant metastasis. Also a squamous cell carcinoma often originates from an in situ dysplastic lesion and a basal cell carcinoma does not. Some common etiologies of squamous cell carcinomas include chronic exposure to UV radiation as well as patients previously exposed to human papilloma virus or HPV infection. A squamous cell carcinoma often originates from cellular or epithelial dysplasia which then transitions or has the potential to transition into a squamous cell carcinoma in situ and if untreated that can then transition into an invasive squamous cell carcinoma. These also can develop from a patient that is dealing with chronic inflammation, whether it be from a chronic wound or sinus tract from chronic osteomyelitis and it also can evolve from burn injury to the skin. Actinic keratoses fall into the category of premalignant lesions. These have the potential to transition and transform into a squamous cell carcinoma. It should be understood that a majority of actinic keratoses do not transition into an invasive squamous cell carcinoma; however, a majority of squamous cell carcinomas do originate from a premalignant lesion. The keratinocyte is a cell of origin of actinic keratosis as well as photo damaged skin. Photo damaged skin again as seen on the progression on the bottom of the slide can transition into an actinic keratosis, if untreated and undiagnosed, can transition into a squamous cell carcinoma in situ also called Bowen's disease and that can then transition into an invasive squamous cell carcinoma.

[12:07]

Clinically, actinic keratosis often present on UV exposed location such as the face and appear as an erythematous papule or a thin plaque with a well-adherent coarse scaling present on the base of the lesion. These lesions often are less than 1 cm in size. They often can be diagnosed with palpation; however, biopsy will reveal the diagnosis of this condition. Again, as stated on the previous slide, approximately 8% of actinic keratoses do have the potential to transform into a squamous cell carcinoma. Some risk factors for this transformation from an actinic keratosis to a squamous cell carcinoma include a patient with a history of skin cancer, patient with long-term cumulative UV radiation exposure, a patient with genetic susceptibility, a patient with an immunosuppressed status or a transplant patient or a patient with a skin phototype 1 or 2 in which they are white skin, minimal tans, and always burns. When treatment is indicated for actinic keratosis, often liquid nitrogen cryotherapy is an effective treatment plan. Squamous cell carcinoma in situ also known as Bowen's disease is a cancerous progression from the precancerous lesions discussed on the previous slide. Clinically, this might present as a maculopapular plaque as well as it may be solitary or multiple in presentation. They appear as a well-demarcated area of scaling or hyperkeratosis with a rough surface. Squamous cell carcinomas arise from epithelial dysplastic lesions and are confined to the epidermis if they are still considered in situ. The term in sit is defined as it remained within the cell of origin. So a squamous cell carcinoma in situ is a malignancy of the keratinocyte still confined within the epidermis.

[14:05]

As a squamous cell carcinoma in situ starts to involve deeper layers of the skin including the papillary dermis and the reticular dermis or deeper tissue layers, this would then be considered an invasive squamous cell carcinoma. Clinically, when we start to see elevation or nodular appearance within an otherwise flat lesion, again that's a clinical finding consistent with likely invasive nature of the carcinoma. Clark's level is a classification system utilized to classify the layers of skin involvement with pigmented skin lesions with level 1 including the epidermis and level 5 extending all the way down through and into the subcutaneous tissue. As stated on the previous slide, a squamous cell carcinoma may originate from an area of chronic inflamed tissue such as a chronic non-healing ulceration as well as a sinus tract from an underlying osteomyelitis. This would be termed a Marjolin's ulcer. This is a more aggressive variant of squamous cell carcinoma with a high rate of metastases. The clinician should be mindful that if a wound is not progressing as planned with appropriate standard care, a biopsy should be considered. This is a clinical photograph of a non-healing ulceration at the medial aspect of the right ankle of a type 2 diabetic male. Upon initial presentation to our wound center, this patient stated that his wound had been present for approximately 5 to 10-years' duration with minimal progression towards healing. Therefore, it was decided upon to perform a punch biopsy to confirm that there has been no malignant transformation of the cells within this ulceration. The next type of epidermal skin cancer that we will discuss is the basal cell carcinoma or the most common type of skin cancer. The cell of origin of the basal cell carcinoma is the basal cells of the epidermis. These are considered locally invasive, aggressive and destructive lesions but have limited ability to metastasize.

[16:05]

The growth of tumors is dependent on stromal cells. The stromal cells provide growth factors allow for growth and spreading of these lesions. Basal cell carcinomas disseminate without their stroma and therefore do not have the ability to grow distal from the original site of involvement. Basal cell carcinomas again have no known in situ phase. A 40% of patients with one basal cell carcinoma will develop another lesion within five years. There are five clinical types of basal cell carcinoma with nodular basal cell carcinoma being the most common. From an epidemiological standpoint, males are more often infected than females. Age greater than 40 is most common onset with 55 to 75 being the most common demographic involved with basal cell carcinomas. Three in 10 Caucasians will have a basal cell carcinoma during their lifetime. From an etiological standpoint, chronic UV radiation can induce DNA damage to the skin causing a patient to be more susceptible to the development of cell dysplasia in a basal cell carcinoma development. Again, patients with skin phototypes 1 and 2 are most at risk including patients that have white skin, always burn and have minimal-to-no tanning. Finally, we will take time to review melanomas. Melanomas are considered a malignant tumor of melanocytes located at the dermal, epidermal junction. The incidents of melanomas are increasing faster than any other preventable cancer in the United States and the incidents has doubled in the last 10 years. In 2014, it was estimated that there were greater than 76,000 cases diagnosed. In 2012, one in 50 people were diagnosed with melanoma. Compared that to 1935, one in 1500 people were diagnosed with melanoma.

[18:00]

It's the most common skin cancer causing fatality and the most cancer in young adults, especially females aged 25 to 29. This is the fifth most common cancer in men and seventh in women and 5% of melanomas are located on the foot. Early recognition of melanomas is critical. Educating patients and stressing detection of these lesions is critical in catching them early as there is a high cure rate, if they are caught during the radial growth phase before they become invasive and start involving the dermal tissue layers. A 30% of melanomas do originate from a preexisting atypical melanocytic lesion; however, 70% of melanomas arise from normal appearing skin. Melanomas typically begin with an initial radial growth phase where they grow horizontally within the epidermal tissue and this was followed by a vertical growth phase where it becomes invasive and starts growing within the dermal tissue. Therefore, we need to catch these during the radial growth phase when the lesion is thin and still considered confined and in situ. When it's confined to the epidermis, it's confined to avascular tissue with a low risk of metastasis. Risk factors for the development of melanoma include intermittent burning especially in patients younger than 14 years of age. There also is a genetic predisposition to developing a melanoma as there is a faulty gene that can be inherited that induces apoptosis in cells that have dysplasia. Other risk factors include the number of atypical nevi as 30% of melanomas do arise from an atypical nevus. A previous history of melanoma poses a 5% risk of developing another melanoma within the patient's life. Again, phenotypic traits including skin phototypes 1 and 2 where there is white skin with patients always burning and minimal-to-no tan development.

[20:08]

When evaluating skin lesions, the clinician should remember the acronym ABCD. This stands for A for asymmetry, in which one side of the lesion does not resemble the other side of the lesion and irregular or notched border around the perimeter of the lesion, color variegation including blue, black, brown, pink, tan, white color within the same lesion and increase in diameter of the lesion including greater than 6 mm in diameter or larger than pencil eraser and finally E for evolving or a changing shape within the lesion. Melanomas can be differentiated based on their growth patterns. Melanomas initially begin with a radial growth phase where the melanocytic tissue will be expanding horizontally within the epidermis. At this point, it is still considered minimally invasive in situ with minimal risk of metastases at this time. This initial radial growth phase is then followed by a vertical growth phase with melanocytic lesion or melanoma begins to grow vertically into the dermal tissue layer. Blood vessels present within the dermal tissue make the patient at a much greater risk of developing metastases at this time. The prognosis between the different types of melanoma are based on this radial growth phase and how long the lesion stays within the radial growth phase. For example, the lentigo maligna melanoma may stay in a radial growth pattern for many years as compared to the nodular melanoma that might begin to grow vertically almost immediately. Clinically, when a melanoma is in the radial growth phase, it is typically a macular presentation or flat. As papular or nodular changes develop within the lesion, often there is a vertical growth component to the melanoma.

[22:01]

The five different types of melanoma that will be reviewed are the lentigo maligna melanoma, nodular melanoma, superficial spreading melanoma, acral lentiginous melanoma and amelanotic melanoma. The amelanotic melanoma is the type that presents without the typical pigmentation seen within the melanoma skin cancers. This is the clinical photograph of a skin lesion at the distal aspect of the left second toe of a 55-year-old Caucasian male. The patient states he thinks he stubbed his toe and developed a bruise at the end of the second digit, however, after six plus months and the lesion has not resolved, he then presented for evaluation. Upon performing a skin biopsy, it was determined that this was actually a melanoma in situ. The melanoma in situ is primarily a histopathological diagnosis where melanoma cells are confined to the avascular epidermis. There is no basement membrane involvement and no dermal tissue involvement with these conditions. The melanoma cells may spread along the basal layer or may be distributed upwardly throughout the epidermis. This is termed pagetoid spreading. Again, this is a histological finding. Technically, every melanoma beings in situ as a macular presentation. Again, the growth pattern does differentiate based on the type of melanoma where some melanomas will stay confined to the epidermis for a long period of time and others might start growing vertically into the vascularized dermis much more quickly. The melanoma in situ is only detectable when radial growth phase is long enough to become visible. The skin lesions will present in an atypical fashion with irregular borders and again color variation within the lesion itself. The lentigo maligna melanoma is the least common type of melanoma representing only about 5% of the melanomas.

[24:02]

However, it is the slowest growing and least likely to metastasize. The radial growth phase can last up to 20 years in some patients. This often presents in older patients greater than 60 years of age on chronically sun-exposed areas. These typically begin as a macular clinical appearance, however, if there is a papular or nodular area within the lesion, this represents conversion from the radial growth pattern to the vertical growth phase demonstrating an invasion into the dermis. The most common type of melanoma to present is a superficial spreading melanoma representing about 70% of melanomas. This also is a slow growing lesion and the radial growth phase may last for many months to up to two years in duration. The morphology of these lesions is often an elevated plaque with color variation within the lesion and commonly presents on the back in men as well as back and/or legs in women. These are more common in females as well as Caucasian with the age of onset between 30 to 50 years of age. Some risk factors for the development of a superficial spreading melanoma include a family history, a history of multiple atypical melanocytic nevi, patients with skin phototypes 1 or 2 or patients with excessive exposure to UV radiation especially during the adolescent years. The worst prognosis when considering melanomas is a diagnosis of a nodular melanoma as this tumor essentially begins in a vertical growth phase. It arises from normal skin and typically presents in a uniformly blue or black presentation. There is no or minimal radial growth phase as seen in the lentigo maligna or superficial spreading types of melanoma.

[26:00]

This lesion often presents in the upper back in males as well as lower legs in females. There is no radial growth phase and immediately again begins in a vertical growth pattern. The typical presentation is a patient presenting with a "new mole." Some of the differential diagnoses when considering a nodular melanoma include a patient with a dermal nevus, a pigmented basal cell carcinoma as well as a dermatofibroma. The acral lentiginous melanoma is the most common type of melanoma that presents on the foot as well as periungual location. This type of melanoma does have a genetic predisposition and is most often seen in people of Asian descent, sub Saharan Africans as well as African-Americans. The difference between this type of melanoma is there isn't a direct association with ultraviolent light accumulation and it's more common in patients with darker skin phototypes. It usually presents on the palms of the hands, the soles of the feet as well as the fingernail or toenail beds. The radial growth phase of the acral lentiginous melanoma can last from months to many years in duration. Vertical growth can being early but not typically recognized early, which can lead to a poor prognosis. The acral lentiginous melanoma subungual type is a melanoma of the nail matrix. As the nail grows distally, the pigmented tissue is dragged distally as well creating this longitudinal streak within the nail bed. A positive Hutchinson sign can be seen with this type of melanoma, in which there is pigmentation that is spread to the proximal eponychium as well as the medial or lateral nail folds. Differential diagnosis for this type of melanoma can include a subungual hematoma, a periungual fungal infection as well as a pyogenic granuloma.

[28:01]

Diagnosis can be difficult with this type of melanoma especially considering the fact that one third of the nail unit melanomas can be amelanotic. Finally, amelanotic melanomas are types of melanomas that are absent of pigmentation. The melanoma forms from melanocyte that is void of pigment. This can present clinically as erythematous papules or nodules. They can be lesions that appear similar to other common skin lesions including psoriasis, dermatitis, different types of basal or squamous cell carcinomas. If the clinician is unsure of the diagnosis, biopsy would be indicated. This is a chart comparing the four major types of melanoma including superficial spreading, nodular, lentigo maligna as well as acral lentiginous melanoma. The key difference between these different types of melanomas is the radial growth compared to the vertical growth patterns. It should be understood and remembered that the lentigo maligna can stay within that radial horizontal growth pattern for many years and is the least invasive of all the different types of melanoma. In comparison, the nodular melanoma has an immediate vertical growth phase and starts to become invasive into the vascularized dermal tissue layer almost immediately making this the most dangerous type of melanoma. There are different methods to stage a melanoma including the Breslow's thickness staging, the Clark's cutaneous involvement staging as well as the TNM or tumor node metastasis staging system. The Breslow's thickness is a staging system that measures the depth of melanoma lesion from the granular layer of the epidermis to the deepest portion of the tumor. This is the most important prognostic consideration when attempting to classify a melanoma. Based on the depth of the lesion, it can predict a survival rate for the patient. It can also help clinician determine the most appropriate margins of resection for more definitive treatment of the melanoma lesion and it can also determine if any further diagnostic workup including a sentinel node biopsy is indicated in the treatment plan.

[30:14]

The Clark's classification system is another way to stage melanomas based on the level of cutaneous involvement of the lesion. A stage 1 is considered an in situ lesion confined to the epidermis and clinically presents in a macular form. Stage 2 Clark's is involvement of the papillary dermis where a small papule will develop clinically within the lesion. Stage 3 is when the melanoma lesion involves entire papillary dermis and a larger papule will be developed clinically. Stage 4 would be involvement of the entire dermis down to the reticular layer, in which a nodular formation will be present clinically and finally stage 5 is involvement of subcutaneous tissue. Once melanoma have been diagnosed and appropriately staged based on the Breslow's thickness as well as TNM staging, recommendations for surgical treatment can ensue. Melanoma in situ lesions should be treated with 5-mm resection of normal tissues surrounding the lesion. Melanomas less than 1 mm of thickness should be resected with 1-cm of normal skin margins and melanoma 1 mm to 4 mm in thickness should be resected with 2 cm margins of normal skin. In summary, we reviewed the common pigmented skin lesions that are benign in nature. We discussed the precancerous lesions as well as the epidermal skin cancers including squamous and basal cell carcinomas as well as melanomas. Once again thank you for your attention.


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