A 13-year-old red-haired female with a family history of melanoma in her father and multiple moles presents for a routine physical and is found to have a thin 8 mm pink papule on the right neck that has appeared in the last 6 months and occasionally bleeds when it rubs on a shirt (Figure 147-1). A narrow margin excisional biopsy was performed which revealed invasive melanoma 0.7 mm in depth with 2 mitoses per high power field. She was referred to pediatric surgery where she underwent wide local excision and sentinel lymph node biopsy of the neck, which revealed micrometastasis in one node. After PET scan showed no distant metastasis, she underwent lymph node dissection and was enrolled in a clinical trial through a major referral hospital in the region. Her prognosis is guarded, but similar to adults with the same cancer stage.
Amelanotic nodular melanoma with atypical vascular structures seen on dermoscopy (see inset in upper left corner). (Used with permission from Ashfaq A.Marghoob, MD.)
Although extremely rare, malignant melanoma is the most common skin cancer in children and represents 1 percent of all new cases of melanoma.1
Between 1973 and 2009, 1230 children in the US were diagnosed with melanoma at a rate of 6 per million overall. Children aged 0 to 9 had the lowest rate at 1.1 per million while children aged 15 to 19 were diagnosed at the highest rate of 18 cases per million.1
Melanoma incidence is on the rise in adults and children with the incidence increasing in children by 2 percent per year and 4 to 8 percent per year in adults.1
In the US, the death rate is decreasing among persons younger than 65.2
The lifetime risk of developing melanoma is 1 in 55 for men and 1 in 36 for women.3
Risk factors can be broadly thought of as genetic risks, environmental risks, and phenotypic risks—arising from a combination of genetic and environmental risks. For example, a fair skinned child (genetic risk) who gets a sunburn (environmental) is much more likely to develop freckles (phenotypic) and melanoma. Childhood sun exposure is a significant risk factor for developing melanoma as an adult.4
Exposure to sunlight.
History of sunburn doubles the risk of melanoma and is worse at a young age.
History of immunosuppression.
Higher socioeconomic status (likely associated with more frequent opportunity for sunburns).
Fair skin, blue or green eyes, red or blonde hair.
In children, female sex is higher risk, in adulthood, male sex is higher risk.
Melanoma in a first-degree relative.
History of xeroderma pigmentosa or familial atypical mole melanoma syndrome.
Personal history of a BRCA2 mutation confers a high risk of uveal melanoma.5
Congenital nevi (Figure 147-2).
Multiple dysplastic nevi.
Personal history of skin cancer.
A. A 2-year-old boy with a bathing trunk nevus and numerous satellite congenital nevi. He benefits from regular skin screening and mole monitoring. (Used with permission from Richard P. Usatine, MD.) B. A giant bathing trunk nevus noted at birth. The dark black colors and variations in color make this a very concerning congenital nevus. Again, regular skin screening and mole monitoring will be a regular part of his care. (Used with permission from Carrie Griffin, MD.)
Melanoma in children may deviate significantly from the traditional ABCDE criteria used to assess risk of melanoma.6 The traditional ABCDE guidelines are listed below followed by newly proposed guidelines to increase the sensitivity of detecting melanoma in children.
Traditional Abcde Guidelines
ABCDE guidelines for diagnosing melanoma (Figure 147-3).7
Superficial spreading melanoma on the neck demonstrates many traditional ABCDE features of melanoma. (Used with permission from Richard P. Usatine, MD.)
A = Asymmetry. Most early melanomas are asymmetrical—A line through the middle will not create matching halves. Benign nevi are usually round and symmetrical (Figure 147-4).
Marked asymmetry, border irregularity, color variation, and increased diameter characterize this thin melanoma. (Used with permission from Richard P. Usatine, MD.)
B = Border. The borders of early melanomas are often uneven and may have scalloped or notched edges. Benign nevi have smoother, more even borders (Figure 147-4).
C = Color variation. Benign nevi are usually a single shade of brown. Melanomas are often in varied shades of brown, tan, or black, but may also exhibit red, white, or blue (Figures 147-4 and 147-5).
Small 4 × 5 mm melanoma that developed on the back of an 11-year-old boy. This melanoma demonstrated asymmetry and variation in color only. (Used with permission from Kelly M. Cordoro, MD.)
D = Diameter greater than or equal to 6 mm. Melanomas tend to grow larger than most nevi. Note that melanomas in children or adults can present less than 6 mm in diameter (Figure 147-5).
E = Evolving could be in size, shape, symptoms (itching, tenderness), surface (especially bleeding), and shades of color.
Modified ABCD criteria in children were developed and proposed by Cordoro, et al. in a recent large cohort study.6 The criteria were developed from the data presented in Figure 147-6 that compared conventional ABCDE criteria with other presenting features of melanoma in children.
Comparison of conventional ABCDE criteria with other presenting features of melanoma in children. (Used with permission from and copyright Cordoro KM, et al. Pediatric melanoma: Results of a large cohort study and proposal for modified ABCD detection criteria for children. J Am Acad Dermatol. 2013.)
In children, particularly those younger than 13, new ABCD detection criteria are needed as many childhood melanomas present as pink or skin colored uniform bumps. The modified ABCD detection criteria are listed below:
A = Amelanotic lesions are more common in children than adults (Figures 147-1, 147-6, and 147-7).
Amelanotic melanoma that developed in a large congenital melanocytic nevus. The boy was only 16-years old. (Used with permission from Kelly M. Cordoro, MD.)
B = Bleeding, Bump. Suspect any new bleeding papule or macule.
C = Color uniformity may be present in childhood melanoma rather than the color variation that is traditionally associated with melanoma (Figure 147-8).
Spitzoid melanoma on the wrist of a 4-year-old girl. (Used with permission from John L. Pfenninger, MD.)
D = De Novo, any diameter. Any lesion arising out of the blue is suspicious in children.
Conventional subtypes of adult melanomas—superficial spreading, nodular, lentigo maligna melanoma, and acral lentiginous melanoma—are not as relevant in diagnosing childhood melanoma. In contrast, most childhood melanoma—especially in children under 10—is more clinically and histologically ambiguous and defies these classifications.6 Any subtype may be classified as amelanotic when pigment is absent to a degree that the lesion is pink in color. In adults, this is rare, representing less than 5 percent of all melanoma. In children, however, up to 70 percent of melanoma may be amelanotic (Table 147-1).6
TABLE 147-1Melanoma Subtypes Versus Melanoma Subtypes in Children ||Download (.pdf) TABLE 147-1 Melanoma Subtypes Versus Melanoma Subtypes in Children
|Melanoma Subtypes in Adults ||Melanoma Subtypes in Children |
|From most frequent to least frequent ||From most frequent to least frequent. |
|1. Superficial spreading melanoma ||1. Unclassified or ambiguous melanoma represents a large majority of those found in children. Childhood melanoma often defies traditional histologic classification. |
|2. Nodular melanoma ||2. Nodular melanoma is the most common subtype of melanoma in children and is represented by an enlarging papule or nodule. A flat macule that is atypical may be monitored over a short period, but a papule or raised lesion should be biopsied rather than monitored if clinically suspicious. |
|3. Lentigo maligna melanoma ||3. Superficial spreading melanoma has a radial growth pattern prior to vertical invasion. The first sign is the appearance of a flat macule or slightly raised and discolored papule or plaque. Colors may vary and include tan, brown, black, red, blue, or white. These lesions may arise at the edge of an older nevus and can arise anywhere on the body. |
|4. Acral lentiginous melanoma ||4. Spitzoid melanoma presents with features similar to a Spitz nevus with a smooth dome shaped papule or nodule that is hairless and brown or red-brown in color (Figure 147-8). |
|5. Amelanotic melanoma represents less than 5 percent of adult melanomas and present as pink to flesh colored macules or papules that may be easily mistaken for an inflammatory papule or non-melanoma skin cancer. In children, up to 70 percent of melanoma may be amelanotic.6 ||5. Acral lentiginous melanoma of the hands and feet is rare in children. |
Other rare melanoma variants include (1) nevoid melanomas, (2) malignant blue nevus, (3) Desmoplastic/Spindled/Neurotropic Melanoma, (4) Clear Cell Sarcoma (in fact a melanoma), (5) Animal-Type Melanoma, (6) Ocular Melanoma (7) and mucosal (lentiginous) melanoma.8
In children, the most common sites of melanoma are the trunk and lower limbs in females and the head and neck in males.1
Dermoscopy is a useful tool in pigmented lesions in adults and in children, though it is less well characterized in children. Dermoscopy is painless, adds information, and can assist in the decision to biopsy.9 In a prospective study of 401 lesions evaluated for melanoma by experts in dermoscopy, the sensitivity of 66.6 percent with ABCDE criteria improved to 80 percent, and specificity rose from 79.3 to 89.1 percent (Figure 147-9).9
Observe many dermoscopic features of melanoma in this superficial spreading melanoma. This is the dermoscopic view of the melanoma in Figure 147-4. (Used with permission from Richard P. Usatine, MD.)
In a study of dermoscopy done by 60 physicians (35 general practitioners, 10 dermatologists, and 16 dermatology trainees) on unaided photos of 40 lesions using the ABCD rule, the Menzies method, a 7-point checklist, and pattern analysis, the sensitivity rose over the unaided eye.10 In children, melanoma will deviate from the benign dermoscopic patterns and have at least one melanoma specific criteria, most commonly atypical vascular structure and crystalline structure (Figure 147-1).11
Accepted dermoscopic local features of melanoma include:
Atypical network (includes branched-streaks).
Streaks—Pseudopods and radial streaming.
Atypical dots and globules.
Negative pigment network.
Blotch (off center).
Blue-white veil/peppering over macular areas (regression).
Blue-white veil over raised areas.
Peripheral tan/brown structureless areas.
Figure 147-8 demonstrates a number of these features.
In children, melanoma diagnosis is often delayed because of the rarity of the diagnosis and a natural tendency to avoid biopsy. Still, a full thickness skin biopsy remains the gold standard for diagnosing melanoma. Complete excisional biopsy with close margins (2 mm) is ideal for histologic diagnosis and tumor staging. Although there is evidence that an incisional biopsy of a portion of a melanoma does not worsen the prognosis, this should only be the rare case when a lesion is too large to excise in the office. When the clinical impression differs markedly from the pathology report, discuss the case with the reading pathologist and share clinical photos if you haven’t done so already. You may need to have the pathologist prepare “deeper sections” or “step sections”—meaning more slices from the same “loaf of bread.” Additionally, if the diagnosis of melanoma was expected and the result of an incisional biopsy does not meet the expectation, go forward with a complete excision or refer to a surgeon who can.
The National Comprehensive Cancer Network (NCCN) Melanoma Guidelines on the Principles of Biopsy state:12
Excisional biopsy (elliptical, punch [when whole lesion is small], or saucerization) with 1- to 3-mm margins is preferred. Avoid wider margins to permit accurate subsequent lymphatic mapping.
The orientation of the biopsy should be planned with definitive wide excision in mind.
Full-thickness incisional or punch biopsy of clinically thickest portion of the lesion is acceptable in certain anatomic areas (e.g., palm/sole, digit, face, and ear) or for very large lesions.
Shave biopsy (not saucerization or deep shave) may compromise pathologic diagnosis and complete assessment of Breslow thickness, but is acceptable when the index of suspicion is low.13
Despite strong opinions about biopsy technique, there is evidence that a scoop shave biopsy leads to an accurate diagnosis and staging 97 percent of the time.13 Still, a shallow shave biopsy may miss important staging information and may cause “upstaging” and unnecessary lymph node biopsy.
Nevi of all types may mimic melanoma. In children, because of the high percentage of melanomas that are melanocytic, broaden the differential to include many inflammatory and vascular papules. Nevi of all types can mimic melanoma. Congenital nevi can be especially large and asymmetrical. Therefore, it is important to ask the patient if the pigmented area has been there from birth and consider how it has changed over time.
Atypical nevi, also called dysplastic nevi, often mimic melanoma (Figure 147-10). When an atypical nevus is suspicious for melanoma, perform a full thickness biopsy or a broad scoop shave for histology. Only the less suspicious dysplastic nevi should be followed with photography or serial exams.
Epidermal nevi are warty in appearance and may fall along embryonic cleavage lines. These are benign and not precancerous but may grow rapidly especially during puberty (Figure 147-11).
Pyogenic granulomas are benign vascular neoplasms that grow rapidly and are often friable. They are frequently associated with pregnancy, but can occur without a clear cause and mimic an amelanotic nodular melanoma (Figures 147-12 and 147-13).
Pseudolymphoma presents as a pink papule or plaque without significant scaling that persists for weeks to months and may be associated with a history of an insect or spider bite (Figure 147-14).
Dermatofibromas are fibrotic nodules that occur most frequently on the legs and arms. They can be any color from skin color to black and often have a brown halo surrounding them. A pinch test will produce a dimpling of the skin in most cases.
Warts in children may mimic melanocytic lesions including Spitz nevi and melanoma (Figures 147-15 and 147-16).
Benign adnexal tumors such as pilomatricomas may appear similar to a nodular melanoma and can occur on the head and neck (Figure 147-17).
This benign compound dysplastic nevus has several features of melanoma including color variation and size greater than 6 mm. (Used with permission from Richard P. Usatine, MD.)
These epidermal nevi were increasing in size, but are not melanocyctic in origin and have no potential to become melanoma. (Used with permission from Richard P. Usatine, MD.)
This pyogenic granuloma formed rapidly and bled easily on the scalp of this teenager. It was excised and sent for pathology to make sure it was not an amelanotic melanoma. (Used with permission from Richard P. Usatine, MD.)
A pyogenic granuloma on the arm of a young boy mimics an amelanotic melanoma. (Used with permission from Richard P. Usatine, MD.)
This pink nodule developed rapidly on the chin of a 11-year-old girl and did not resolve after several months. Pathology was consistent with pseudolymphoma. (Used with permission from Richard P. Usatine, MD.)
This pink and black wart with dotted vessels appeared suddenly on the leg of a teenage boy and shares some features of melanoma. (A) Clinical (B) Dermoscopy. (Used with permission from Jonathan B. Karnes, MD.)
A and B. This papule appeared most consistent with a Spitz nevus, but histology revealed a wart with unusual pseudoepitheliomatous hyperplasia. (Used with permission from Jonathan B. Karnes, MD.)
A pink and purple nodule on the nose that had grown over several months. This was excised and turned out to be a benign pilomatricoma. This is clinically suspected when rock hard calcifications are palpable within the tumor. (Used with permission from Richard P. Usatine, MD.)
Cutaneous melanoma is surgically treated with complete full skin depth excision using margins determined by the Breslow depth. This depth is a measure of tumor thickness from the granular layer of the epidermis to the point of deepest invasion using an ocular micrometer.
Current recommendations for excision margins range from 5 mm for in situ lesions to 1 to 2 cm for invasive lesions. A recent study showed significant benefit with a 9 mm margin on Mohs excision of melanoma in situ compared with 6 mm margins at a referral center.14
Sentinel lymph node biopsies are recommended for tumors of greater than or equal to 1 mm in depth (Figure 147-18) and should be considered for thinner lesions with ulceration or more than 1 mitosis per mm2. Even in patients with thin melanoma with mitoses above 1 per mm2 sentinel lymph node biopsy should be considered according to the most recent guidelines.15 In these guidelines, mitoses per mm2 has replaced Clark’s levels to distinguish T1a from T1b tumors.15
Melanoma staging takes into account tumor thickness and metastasis and prognosis worsens statistically with each increasing stage from 0 to IV. A patient with an in situ melanoma and no nodal metastasis is considered stage 0. Thicker tumors that remain localized to the skin may be staged as high as stage IIC and subcategories are based on tumor thickness and presence of ulceration. Any lymph node metastasis is considered stage III or higher and any distant metastasis beyond lymph nodes is categorized as stage IV.16
Patients with advanced melanoma should be referred to medical oncology and may receive combination therapy with multiple chemotherapeutic agents and immunotherapy. Many trials are ongoing and three new drugs including interferon 2-alpha, vemurafenib, and ipilimumab have been approved for use in advanced melanoma. Treatment regimens in children are similar to regimens in adults.
Recently two new chemotherapeutic agents have been FDA approved for the treatment of metastatic melanoma. One, vemurafenib is a monoclonal antibody targeting the BRAF mutation expressed on many melanomas. Ipilimumaub prevents dampening of the immune system by blocking a regulatory molecule CTLA-4. Both of these medications used in combination with dacarbazine have shown a small but significant increase in progression free survival in adults and are in ongoing trials in children.17
Thick ulcerated nodular melanoma on the back was mostly amelanotic in appearance. The melanoma depth was greater than 1 mm and the patient was sent for a complete excision with a sentinel node biopsy. (Used with permission from Richard P. Usatine, MD.)
The need for follow-up is largely determined by the stage of the disease. Updates to the staging criteria are published by the American Joint Committee. As previously mentioned, the prognosis is worsened by increasing depth, mitotic rate, ulceration, positive lymph nodes, and metastases.
The follow-up for stage 0 and 1 cutaneous melanoma includes regular skin examinations by a physician trained in skin screening. Total body photography is available in limited areas, but may be of benefit in monitoring patients with multiple nevi. The rate of subsequent cutaneous melanomas among persons with a history of melanoma was found to be more than 10 times the rate of a first cutaneous melanoma and the highest incidence of recurrence was in the first 3 to 5 years after initial diagnosis.18,19
Advise patients to avoid future sun exposure and monitor their skin for new and changing moles. Advise avoidance of artificial tanning. Recommend a complete skin examination yearly by a physician trained to detect early melanoma. A large portion of adult melanoma is caused from childhood exposure.4
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. Childhood sun exposure as a risk factor for melanoma: a systematic review of epidemiologic studies. Cancer Causes Control. 2001;12(1):69–82.
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