Melanoma 01-21 Flashcards
A newborn is evaluated for a congenital melanocytic nevus encompassing the right temporal and parietal scalp and the right hemiface, sparing the nose and lips. There is no family history of melanoma. The parents are interested in discussing treatment options for this condition and ask about the risk of malignant transformation. Which of the following is the approximate risk of melanoma in this patient?
A) 2%
B) 10%
C) 15%
D) 20%
The correct response is Option A.
Multiple studies have shown that surgical treatment of giant congenital melanocytic nevi does not reduce the risk of melanoma. Overall, the risk of melanoma in this population ranges from 0.7 to 2.9% compared with the 0.6% melanoma risk in the general population. The total number of cases of giant congenital melanocytic nevi is small, as this is a rare condition, and most of these cases do not go on to develop melanoma. Rather, melanoma appears to be generic biologic risk rather than related to the nevus itself. The risk of melanoma is highest in trunk lesions rather than other areas of the body. Furthermore, melanoma does not always occur in the giant congenital nevus itself, but may arise from a satellite lesion instead.
Cutaneous melanomas arise in which of the following epidermal layers?
A) Stratum basale
B) Stratum corneum
C) Stratum granulosum
D) Stratum lucidum
E) Stratum spinosum
The correct response is Option A.
Melanomas arise from melanocytes in the stratum basale. The epidermis comprises four layers, from deep to superficial: stratum basale, stratum spinosum, stratum granulosum, and stratum corneum. Glabrous skin has an additional layer between the stratum granulosum and stratum corneum called stratum lucidum. The stratum basale consists of basal cells. These are stem cells that differentiate into keratinocytes, which then migrate upward. In the stratum spinosum, the keratinocytes form intercellular connections via desmosomes. In the stratum granulosum, the keratinocytes have keratohyalin granules. In the stratum corneum, the cells are compact and surrounded by a lipid layer, thus giving the skin its barrier function.
Merkel cells are found in the stratum basale. Langerhans cells are found in the stratum spinosum, stratum granulosum and the dermis.
Basal cell carcinomas arise from basal cells in the stratum basale.
An 80-year-old woman has been diagnosed with lentigo maligna of the cheek. The patient refuses surgical excision. Which of the following is the most appropriate treatment option?
A) Cryotherapy
B) Electrodessication and curettage
C) Laser removal
D) Topical 5-fluorouracil
E) Topical 5% imiquimod
The correct response is Option E.
Lentigo maligna is the most common type of cutaneous melanoma in situ. It arises in chronically sun-exposed areas such as the face and neck. The lifetime risk of development into invasive lentigo maligna melanoma is approximately 5%. Treatment is excision with 5- to 10-mm margins. Surgical excision is the treatment of choice as it allows assessment of margins. Moreover, up to a third of all lentigo maligna specimens are upstaged to invasive melanoma after definitive excision. For patients who are not candidates for surgery, second-line treatment options are radiation and topical 5% imiquimod.
Imiquimod is an immune response modifier. It induces the immune system by acting on toll-like receptor 7. Imiquimod has a clearance rate of 50 to 93% and a recurrence rate of 24.5% for lentigo maligna. It can also be used for positive or close margins after excision, when re-excision is not possible or would result in unacceptable morbidity. Imiquimod is also used for treatment of warts, actinic keratosis, and basal cell carcinoma.
Topical 5-fluorouracil, cryotherapy, electrodessication and curettage, and laser do not have high-quality data supporting their efficacy in lentigo maligna. They are therefore not good treatment options.
A 53-year-old African American man is referred for evaluation of a 3-mm-wide pigmented streak of the left index fingernail. A full-thickness biopsy of the nail matrix confirms the diagnosis of melanoma. Which of the following factors is most pertinent in determining prognosis and 5-year survival in this patient?
A) Mitotic rate
B) Tumor free resection margins
C) Tumor location
D) Tumor stage
E) Width of the lesion
The correct response is Option D.
This patient has acral lentiginous melanoma (ALM) based on the clinical description of a dark-skinned man with a tumor on the fingernail presenting as a pigmented streak. The prognosis for ALM is typically worse than other melanoma subtypes. The poor survival rate of these patients may be due to a delay in diagnosis. As in other melanoma subtypes, tumor thickness is the most important prognostic indicator. Overall, 5-year survival for ALM is 80 versus 91% for all melanomas. Acral lentiginous melanoma is the least common subtype of melanoma, however, it makes up the highest percentage of cutaneous melanomas in dark-skinned patients. ALM is predominantly found on the palms, soles, and nail beds. This is in contrast with other melanoma subtypes that typically occur in sun-exposed areas. However, the location of the tumor does not directly influence the prognosis. It is more correlated to diagnosis at a later stage.
Mitotic rate and other pathologic characteristics such as microscopic ulceration, lymphatic, or nerve involvement can upstage the tumor. However, it is not the primary determinant of tumor stage, and mitotic rate is no longer considered as part of staging in early melanomas.
Achieving adequate resection margins in ALM may be difficult, especially in tumors involving the nail unit. Amputation at the next most proximal joint is often recommended. Regardless of the status of the margins, prognosis is still determined by depth at diagnosis. Thicker tumors have a higher incidence of nodal involvement and metastatic disease. In later stage disease, surgical resection of the primary tumor is for diagnostic purposes, local control, and occasionally palliative care.
Pigmented lesions of the nails greater than 2 mm have a higher likelihood of being invasive melanoma, but width of the lesion is not involved in tumor staging or prognosis.
A 67-year-old woman presents with a 7-mm, irregular, asymmetrical, heterogeneous brown macule that has been enlarging for the past 2 months. An excisional biopsy with 2-mm margins shows melanoma. After tumor thickness, which of the following pathologic features is most indicative of her prognosis?
A) Clark level
B) Macule diameter
C) Mitotic rate
D) Morpheaform features
E) Ulceration
The correct response is Option E.
This lesion has all of the clinical features suggestive of melanoma: asymmery, irregular border, heterogeneous color, diameter greater than 6 mm, and evolution. After thickness, ulceration is the most important prognostic indicator for melanoma, and has become an important component of T staging. The prior AJCC staging system did consider mitotic rate but recent evidence has shown that ulceration is a more important prognostic indicator. Mitotic rate is no longer a factor in determining T stage, whereas ulceration is. Clark level and lesion diameter are not independent predictors of outcome for melanoma. Morpheaform features are associated with poorer outcomes in basal cell carcinoma.
A 55-year-old Caucasian man comes to the office for evaluation of a pigmented streak of the left thumb and index fingernails. Medical history includes a minor crush injury to the thumb one year ago that required no treatment. Examination shows a 4-mm-wide pigmented streak in both digits that extends from the eponychial fold to the tip of the sterile matrix. The patient reports that the pigmented areas have become darker over time. Which of the following clinical features is most consistent with a benign lesion?
A) Age greater than 50 years
B) Change in color over time
C) Involvement of more than one digit
D) Pigmentation involving the periungual skin
E) Width greater than 3 mm
The correct response is Option C.
Subungual melanoma is a relatively rare melanoma subtype accounting for 0.7 to 3.5% of all melanomas. Because of the location, appearance, and unique anatomy of the nail unit, subungual melanomas are often diagnosed late in more advanced stages than typical cutaneous melanoma. There is disagreement as to whether subungual melanomas behave more aggressively than cutaneous melanomas of comparable depth. In addition, it can be difficult to distinguish subungual melanomas from benign melanonychia.
Characteristics that are concerning for subungual melanoma are: age 50 to 70, longitudinal band greater than 3 mm or irregular border, change of lesion size or coloration, extension onto periungual skin (Hutchinson sign), personal or family history of melanoma, and single finger involvement.
Benign melanonychia is more common in dark-skinned patients. The differential diagnosis of subungual pigmentation includes subungual hematoma, onychomycosis, and Addison disease among others.
In this case, multiple digit involvement is the clue that the lesions are benign. All other characteristics could be consistent with malignant melanoma. If there is concern for subungual melanoma, a full-thickness biopsy of the pigmented area should be performed.
An otherwise healthy 2-year-old male infant is evaluated because of a congenital melanocytic nevus on his flank. Physical examination shows a hairy, 10 x 5-cm nevus with areas of dark brown pigmentation that is growing proportionate to the infant’s growth rate. He has another nevus, which measures less than 2 cm, on his arm. Which of the following is the primary indication for excision?
A) Dark color
B) Growth rate
C) Presence of hair
D) Presence of two lesions
E) Size of lesion
The correct response is Option E.
The primary indication for excision in this case is the 10-cm measurement in greatest dimension. This makes this congenital nevus a giant nevus. The exact definition of a giant nevus has been debated, but one of the most constant definitions is a nevus that is 20 cm in greatest dimension in an adult or a nevus that will become 20 cm in greatest dimension once the child is fully grown. This latter measurement usually translates to approximately a 9-cm nevus on the head and neck, or approximately a 6-cm nevus on the body of an infant. Other definitions of giant nevi include a nevus that is about 1% of the body surface area in the head and neck region or 2% of the body surface area in the trunk region, a nevus that is greater than 100 cm2 in area, or a nevus that cannot be excised in one stage. The main indication for excision in these giant congenital nevi is the malignant potential that they harbor. The rates of malignant degeneration are also a matter of great debate, with rates quoted anywhere from 0 to 40%. More recently, however, rates of less than 5% are quoted.
The other clinical features are not risk factors that indicate excision of the nevus. If a patient has more than three nevi, that potentially does increase the risk for malignant melanoma in the patient; however, this patient has only two.
A 35-year-old primigravid woman at 10 weeks’ gestation is diagnosed with a 1.5-mm deep melanoma of the right cheek. Lymphoscintigraphy is planned. Which of the following is the most appropriate treatment of this patient?
A) Wide local excision during general anesthesia with 0.5-cm margins and concurrent sentinel node biopsy
B) Wide local excision during general anesthesia with 1-cm margins and concurrent sentinel node biopsy
C) Wide local excision during general anesthesia with 2-cm margins and concurrent sentinel node biopsy
D) Wide local excision during local anesthesia with 0.5-cm margins and second trimester sentinel node biopsy
E) Wide local excision during local anesthesia with 1-cm margins and second trimester sentinel node biopsy
The correct response is Option E.
The most recent guidelines for nonobstetric surgery during pregnancy from the American College of Obstetricians and Gynecologists Committee on Obstetric Practice (2011) recommend performing nonurgent surgery in the second trimester to minimize the risk of preterm contractions and spontaneous abortion. For patients and physicians who consider these risks unacceptable, then wide local excision with administration of a local anesthetic agent after preoperative lymphoscintigraphy, with delayed sentinel node biopsy during general anesthesia, after delivery, is recommended. For a 1.5-mm melanoma, the excision margin is 1 cm.
A fair-skinned 55-year-old man is evaluated because of an irregular dark lesion on his back. Patient history includes frequent sunburn. On examination, the lesion is 8 mm in size, dome-shaped, dark, and has the appearance of a blood blister. The border of the lesion does not appear irregular. A biopsy of the lesion shows a well circumscribed proliferation of atypical melanocytes extending vertically throughout the dermis. There is no lateral extension of the intra-epidermal component. Which of the following is the most likely melanoma subtype?
A) Acral lentiginous
B) Desmoplastic
C) Lentigo maligna
D) Nodular
E) Superficial spreading
The correct response is Option D.
The most likely subtype of melanoma in this patient is nodular. Nodular melanomas are the second most common subtype (10 to 20%) and are commonly seen in the trunk, head, and neck with a slightly increased incidence in men. Upon invading the dermis, these lesions have a rapid vertical growth phase compared to the radial growth phase of the superficial spreading subtypes. These lesions are often dark and dome-shaped and have the appearance of a blood blister. They have increased metastatic potential. Histologic examination shows a sharply circumscribed epidermal component and extensive dermal proliferation with atypical melanocytes.
The superficial spreading subtype is characterized by lateral spreading of malignant melanocytes in the epidermis. This is the most common subtype and exhibits a prolonged radial growth phase before developing a vertical component. These lesions occur usually on sun-exposed skin and often arise in preexisting nevi. They appear flat and become irregular or raised with growth. Lentigo maligna is a rare form of melanoma with low malignant potential. They often arise from lentigo maligna lesions and grow slowly in a radial fashion before a vertical phase. They are more common in older women and have a strong correlation to sun exposure. They are often present in the face, head, and neck as large, tan lesions with convoluted patterns.
Acral lentiginous melanoma is more common in dark-skinned patients and is often found on the palms, nail bed, and soles of the feet. These lesions are aggressive and frequently metastasize. Desmoplastic melanoma is also a rare subtype with aggressive local growth; however, these lesions rarely metastasize. They are similar in appearance histologically to spindle cell tumors and are confused with common nevi, Spitz nevi, or hemangiomas.
A 63-year-old man is evaluated because of a 1.6-cm pigmented lesion on his right shoulder. Excisional biopsy shows superficial spreading malignant melanoma with a Breslow depth of 3 mm. Evidence of distant metastases to which of the following tissues on further staging carries the poorest prognosis for this disease?
A) Liver
B) Lung
C) Lymph nodes
D) Subcutaneous tissue
The correct response is Option A.
The American Joint Committee on Cancer (AJCC) revised TNM staging of melanoma in 2010. Three subgroups of distant metastases are distinguished: skin and soft-tissue metastases (best prognosis), lung metastases (intermediate prognosis), and other visceral metastases such as liver and brain (worst prognosis). Elevated lactate dehydrogenase in either of the first subgroups up-stages to the last subgroup.
A 4-year-old boy undergoes evaluation of a large congenital melanocytic nevus of the scalp affecting 40% of the surface area. Results of a recent biopsy in the center of the lesion showed diffuse areas of severe dysplasia. Which of the following is the most appropriate management?
A) Serial excision, linear closure
B) Single-stage excision, latissimus dorsi musculocutaneous free flap, skin grafting
C) Single-stage excision, rotational flap closure
D) Tissue expansion, excision, closure
E) Observation
The correct response is Option D.
This patient’s congenital nevus involves 40% of his scalp and has areas of severe dysplasia. Although the lifetime risk of malignant transformation in giant nevi as a whole is approximately 4%, the presence of biopsy-proven severe dysplasia at this young age mandates a more aggressive approach to management than observation. Complete removal of the nevus with reconstruction of the scalp is recommended to prevent malignant conversion. Although serial excision is useful and often preferred for moderate sized lesions, this nevus is far too big to completely excise and close in that fashion. Moreover, the intervals between stages would require more time than tissue expansion, and with the degree of dysplasia present in this patient, this is risky. Similarly, it is dubious if a nevus this size could be successfully excised and closed in one stage using only rotational flaps. In addition, this would alter the direction of the hair. The use of a free flap is far too extreme in the absence of a frank malignancy (which this is not) and would leave this child with a large bald area. The best option is tissue expansion, followed by complete excision and closure, which was successfully employed in this case.
A 62-year-old man has a lesion of the left pinna. Examination of a specimen obtained on biopsy shows a 2.01-mm-thick melanoma with no ulceration, 11 mitoses, and a positive deep margin. The surgeon’s decision to perform sentinel node biopsy is most heavily influenced by which of the following factors?
A) Breslow thickness
B) Head and neck location
C) Lack of ulceration
D) Number of mitoses
E) Positive deep margin
The correct response is Option A.
Head and neck melanomas in general were thought to be distinct from other anatomic sites. Clearly there can be reconstructive and functional issues that are unique, such as in an ear melanoma. In general the first Multicenter Selective Lymphadenectomy Trial (MSLT-1) concluded that for intermediate-thickness melanoma (1-4 mm), the status of the sentinel node was the most powerful predictor of outcome. In an interim report in 2006, well before the final report in 2014, the specifics on what percentage of patients had melanoma of the head and neck in the MSLT-1 trial were not described, but what was reported was a lower rate of identification of a sentinel node in the neck versus lesions that mapped to the groin or axilla. This led many to conclude that the utility of the sentinel node biopsy in the head and neck was in question. More recent data from multiple high-volume institutions have concluded that identification of the sentinel node for head and neck melanoma is as accurate as other sites in the body, including similar false-negative rates and impact on prognostication.
Mitotic rate does not affect staging above 1-mm thick lesions, and although ulceration can, it does not influence the rationale to perform a sentinel node biopsy in intermediate thickness tumors. In thinner melanomas, a positive deep margin may be an indication for a sentinel node biopsy, but not for a tumor greater than 1-mm thick. The fact that lymphoscintigraphy may map the sentinel node to the parotid region means that the surgeon should be prepared to do a parotidectomy with facial nerve preservation, although recently less-invasive techniques have been described.
A 55-year-old man undergoes biopsy of a pigmented lesion on the neck. Examination of a biopsy specimen shows superficial spreading of a malignant melanoma with no ulceration, 1.2-mm thickness, and less than 1 mitosis per mm2. In addition to wide local excision, which of the following is most appropriate treatment?
A) Interferon therapy
B) Radiation therapy
C) Regional lymphadenectomy
D) Sentinel lymph node biopsy
E) Observation
The correct response is Option D.
According to National Comprehensive Cancer Network guidelines, melanomas with Breslow thickness greater than 1 mm should be treated with wide local excision and sentinel lymph node biopsy.
Wide local excision alone, with no additional lymph node sampling, may be appropriate for some melanomas less than 1 mm, but additional factors such as mitotic rate and ulceration should be assessed.
Random lymph node sampling would not necessarily assess the first node in the draining basin, therefore, it is important that the sentinel lymph node be identified with techniques such as tracking of an intradermally injected radionucleotide using a handheld gamma probe and visual identification with blue dye.
In the past, melanomas with thickness between 1 and 4 mm were treated with elective lymph node dissection. Since several randomized, prospective studies failed to clearly demonstrate a survival advantage and the significant associated morbidity, sentinel lymph node biopsy has replaced this procedure.
While there are growing indications for the use of radiation therapy for skin cancers, intraoperative radiation therapy is not routinely used.
A 48-year-old right-hand–dominant man is referred for treatment of a biopsy-proven subungual malignant melanoma in situ of the right thumb. Which of the following is the most appropriate treatment?
A) Amputation to the interphalangeal joint with no reconstruction
B) Amputation to the metacarpophalangeal joint with toe-to-thumb transfer
C) Chemotherapy
D) Radiation therapy
E) Wide local excision with split-thickness skin grafting
The correct response is Option E.
While the literature lacks randomized control data, there is mounting evidence that melanoma in situ can be appropriately treated with wide local excision alone. This is associated with considerably less morbidity than amputation with or without reconstruction. Radiation therapy or chemotherapy are not appropriate treatment options for malignant melanoma in this setting.
A 2-month-old female infant is evaluated because of a pigmented skin lesion on the midline lumbar region. Physical examination shows a dark brown lesion that is 10 cm in diameter with an irregular surface and coarse hairs. This patient is at increased risk for which of the following?
A) Basal cell carcinoma
B) Occult spina bifida
C) Precocious puberty
D) Renal anomalies
E) Vascular malformations
The correct response is Option B.
The lesion described is a congenital melanocytic nevus (CMN). Basal cell carcinomas are associated with nevus sebaceous. Precocious puberty is seen in congenital adrenal hyperplasia, which is associated with generalized hyperpigmentation most apparent in the areolas and genitalia. Renal anomalies and vascular malformations are not associated with CMN. Abnormalities of the vertebral column including spina bifida are seen with CMN overlying the spine. These lesions are also associated with neurocutaneous melanosis.
A 67-year-old man with a large lentigo maligna on the left cheek comes to the office for closure after undergoing excision. Which of the following steps is most appropriate for the surgeon prior to performing a cervical-facial rotation flap?
A) Await permanent pathology results
B) Confirm negative margins by Mohs micrographic surgery
C) Evaluate the margins clinically with a Wood lamp
D) Perform confocal microscopy
E) Refer the patient for sentinel node biopsy
The correct response is Option A.
Lentigo maligna is a slow-growing lesion with a substantial radial growth pattern before progressing to invasion in most cases. These lesions often occur in the head and neck region of older patients with a history of sun exposure. Clinical occurrence is variable, but many appear as irregular, sometimes extensive, pigmented patches on the face. Staging of these lesions follows the American Joint Committee on Cancer guidelines, and prognosis is based on depth of invasion. Need for sentinel node biopsy is based on staging and is independent of resection size.
Wide local excision of the lesion is the current standard of care, but the surgical margin for successful excision remains controversial. Alternative techniques have been investigated to improve the 8 to 20% recurrence rates associated with standard excision with 5-mm margins. Mohs micrographic surgery shows promise in the treatment of this disease, but there remains difficulty in interpretation of melanocyte proliferation on frozen section, leading to the proposal of modifications of the procedure, including sending the final Mohs margins for rush permanent section evaluation for verification of clear margins, the so-called “slow Mohs.”
Clinical evaluation of margins with Wood lamp may be useful in evaluating the clinical extent of the lesion but is not adequate for determination of surgical margins. Confocal microscopy is a new technique that allows examination of melanocytes without biopsy. This modality may be useful in diagnosis of lentigo maligna, but availability is currently limited and requires training in interpretation of images.
An 88-year-old woman comes to the office because of the 2-cm pigmented lesion on the vertex of the scalp shown. There is no evidence of cervical or suboccipital lymphadenopathy. Examination of a specimen obtained on punch biopsy shows a Breslow thickness of 2.1 mm, Clark Level IV, two mitotic figures per high-power field, and no evidence of ulceration. Which of the following is the most appropriate management?
A) Excision with 1-cm margins and bilateral cervical lymphadenectomy
B) Excision with 2-cm margins and delayed sentinel lymph node biopsy
C) Excision with 3-cm margins and bilateral cervical lymphadenectomy
D) Preoperative lymphoscintigraphy, excision with 1-cm margins, and immediate sentinel lymph node biopsy
E) Preoperative lymphoscintigraphy, excision with 2-cm margins, and immediate sentinel lymph node biopsy
The correct response is Option E.
In the patient described with an intermediate thickness tumor (1–4 mm) and clinically negative neck, the most appropriate treatment is wide excision with 2-cm margins (shown) and a concurrent sentinel lymph node biopsy. The defect may be reconstructed with a local flap or skin graft depending on patient and surgeon preference. In Stage I and II melanomas (localized disease T1-4, and no evidence of regional lymphadenopathy, N0), Breslow tumor thickness is the most important predictor of local recurrence, regional/distant metastases, and overall survival.
Current recommended excisional margins are 0.5 to 1.0 cm for melanoma in situ/lentigo maligna. For invasive lesions less than 1 mm thick, a 1-cm margin is adequate. Lesions with Breslow thickness of 1 to 2 mm should be resected with a 1- to 2-cm margin, using closer to 2 cm when the anatomical area is more forgiving (scalp/trunk), the thickness approaches 2 mm, or the lesion displays more aggressive histopathologic features, such as ulceration, lymphovascular invasion, tumor regression, or a mitotic index greater than one figure per high-power field. Lesions between 2 to 4 mm are adequately treated with 2-cm margins. Balch, et al., have shown that 2-cm margins are safe for lesions of intermediate thickness with equivalent survival rates, less use of skin grafting, shorter hospital stays, and lower medical costs when compared with more aggressive peripheral margins. When possible, 3-cm margins should be used for tumors greater than 4 mm thick because of their high local recurrence rate (greater than 20%).
Patients with intermediate-thickness melanomas have a 20 to 25% chance of microscopic regional disease. Before the advent of sentinel lymph node biopsy, elective lymphadenectomy (ELD) was advocated for patients with intermediate-thickness melanoma because of a significant improvement in overall survival at 10 years. The primary disadvantage of routine ELD, however, was that approximately 75 to 80% of patients underwent an unnecessary procedure.
The status of the sentinel lymph node is a powerful predictor of survival in melanoma because it identifies (1) those patients with a relatively favorable prognosis requiring no further therapy; and (2) high-risk patients who might benefit from additional surgery (completion lymphadenectomy) and interferon. Current indications for sentinel lymph node biopsy include all of the following: male patients with truncal melanoma less than 0.76 mm thick (9% incidence of nodal metastasis); all patients with melanoma thickness 0.76 to 1.0 mm (5% incidence of nodal metastasis); male patients with “thin” melanomas with aggressive features (Clark Level III or greater, ulcerated, evidence of regression, or axial location; these patients have a 10% risk of metastasis); and all melanomas greater than 1 mm in thickness.
In the scenario described, 1-cm margins would be too narrow. A 3-cm margin is excessive for the lesion described. As noted, elective lymphadenectomy has been replaced with sentinel lymph node biopsy in a clinically negative neck. Finally, sentinel lymph node biopsy should be performed at the time of the primary tumor resection if possible due to variations in the lymphatic drainage that may occur after wide excision, skin grafting, or flap closure.
A 60-year-old man comes to the office because of a 2-cm pigmented lesion on the right lower back (shown) that has enlarged progressively for 3 years. No lymph nodes are palpable. Examination of a specimen obtained on punch biopsy shows a Clark Level IV malignant melanoma with a Breslow thickness of 1.2 mm and ulceration. Which of the following is the most appropriate management?
A) Excision with 2-cm margins
B) Preoperative lymphoscintigraphy, sentinel lymph node biopsy, and excision with 1-cm margins
C) Preoperative lymphoscintigraphy, sentinel lymph node biopsy, and excision with 2-cm margins
D) Excision with 1-cm margins, followed by lymphoscintigraphy and sentinel lymph node biopsy at a later date
E) Excision with 3-cm margins, split-thickness skin grafting, and right axillary lymph node dissection
The correct response is Option C.
A melanoma 1.2 mm in thickness on the lower back would best be excised with 2-cm margins and a concurrent sentinel lymph node biopsy. Although a few studies cite the adequacy of a 1-cm margin for tumors less than 2 mm in thickness, a punch biopsy was performed in the scenario described, and the final pathology of the complete lesion could show a thicker lesion. In a location where there is sufficient tissue, a 2-cm margin is more appropriate for a lesion that is over 1 mm in thickness. Most authors cite resection margins of 5 mm for melanoma in situ, 1 cm for melanoma less than 0.8 mm, and 2 cm for melanoma between 0.8 and 4 mm.
Patients with intermediate thickness lesions of 0.8 mm to 4 mm have a 20 to 25% incidence of microscopic regional disease. Sentinel lymphadenectomy serves to identify patients at high risk who may be candidates for adjuvant treatment. At this time, sentinel lymph node biopsy is a diagnostic, but not yet proven, therapeutic procedure.
In patients with melanomas greater than or equal to 1 mm in thickness and no clinical evidence of regional lymph node metastases, lymphoscintigraphy is performed preoperatively to define the lymphatic drainage and demonstrate sentinel lymph node location. Sentinel lymphadenectomy is performed most accurately at the time of wide and deep excision of the primary lesion. Later, sentinel lymph node localization may be impaired if the primary lesion has been excised deeply, as the drainage patterns may have been altered by the previous procedure.
It is imperative to obtain preoperative lymphoscintigraphy in areas with a high likelihood of aberrant drainage patterns. In the trunk, unpredictable drainage patterns can occur in 20 to 35% of cases.
Which of the following additional findings in the patient shown is indicative of the most life-threatening syndrome?
A ) Hydrocephalus
B ) Large or multiple axial nevi
C ) Posterior midline nevi
D ) €œSatellite € nevi
E ) Underdevelopment of a limb
The correct response is Option A.
This patient has congenital melanocytic nevi (CMN), which are birthmarks that are present at birth or become apparent within the first year of life. They are found in 1% to 2% of the general population. In addition to being cosmetically disfiguring, CMN are one of several known risk factors for development of melanoma.
While the majority of malignant melanomas arise from melanocytes in previously normal skin or within acquired and often atypical (dysplastic) melanocytic nevi, few would dispute the contention that melanomas may arise in CMN. The incidence of such malignant transformation, however, remains a highly controversial topic in cutaneous oncology. It has been estimated that large CMN carry a 4.5% to 10% lifetime risk of melanoma or other neural crest malignancies. While this risk appears to be distributed over the lifetime of the patient, recent studies suggest that it is greatest in early childhood, between birth and 10 years of age, with 50% of the malignancies developing by 5 years of age, and 70% by 10 years of age. Interestingly, 50% of the melanomas that develop occur within the nevi, but the other 50% occur within the central nervous system (CNS) or within normal skin. Despite this significant increase in risk, it should be noted that giant CMN-associated melanomas still account for less than 3% of all pediatric melanomas.
Large CMN may also be associated with symptomatic or asymptomatic systemic abnormalities. Whereas melanocytes in CMN are generally limited to the mid to upper dermis, a subset of giant CMN exhibit melanocytes in the lower third of the dermis, within the subcutaneous fat, and occasionally as deep as the fascia and skeletal muscles possibly causing ipsilateral limb underdevelopment. Large axial CMN have been associated with the syndrome of neurocutaneous melanosis (NCM).
NCM connotes the association of a large axial CMN with the CNS involvement. CNS manifestations may present as hydrocephalus, seizures, focal deficits, or partial paresis. The majority of those children with NCM who manifest such problems do so before 2 years of age. When neurologic symptoms are present, the prognosis is grave. At least two thirds of those who present with or develop symptomatic CNS disease succumb to the disease process, either because of inexorable €œbenign € proliferation of melanocytes in the leptomeninges and brain or as a result of malignant degeneration. Symptomatic hydrocephalus may necessitate the placement of a ventriculoperitoneal or ventriculojugular shunt. Unfortunately, following malignant transformation in the CNS, such shunts afford the malignant melanocytes ready access to the systemic circulation, leading to a rapid demise.
To identify which patients with CMN may have CNS involvement, a number of risk factors have been identified. These include the presence of large or multiple axial CMN or both, nevi on the posterior midline, and the presence of multiple satellite nevi. MRI with gadolinium contrast has proved to be a particularly sensitive method for detecting the presence of CNS involvement by melanocytes in such patients. MRI can detect occult neurologic involvement even in infants who are clinically normal. In addition to meningeal involvement, lesions in the cerebrum, cerebellum, spinal cord, and elsewhere have been detected. The ultimate significance of such radiologically evident lesions in clinically asymptomatic children remains to be determined. The risk of developing NCM must also be a factor in any treatment decision, as the prognosis for children with symptomatic NCM is extremely poor. Since the majority of patients with NCM will succumb to the CNS involvement and not from the nevi themselves, it may be determined that the risk of surgical removal of giant CMN in these patients outweighs the benefits.
In certain children at high risk for the development of NCM (eg, those with large CMN in a posterior axial location in the presence of satellite nevi), and especially in those children with radiologic evidence of CNS involvement, a delay in surgical treatment of the large CMN until 2 years of age (the median age for presentation of neurologic symptoms) might be considered. The prognosis for children with symptomatic CNS involvement is so poor that most are unlikely to survive long enough to succumb to the €œrelatively € low risk of cutaneous melanoma.
A 73 year old man is referred to the office by his primary care physician for evaluation of discoloration of the nail of the left thumb (shown), which has been present for the past seven years. The patient says the appearance of the nail has not changed recently. Biopsy of the nail matrix shows malignant melanoma of indeterminate depth. Which of the following surgical procedures is the most appropriate management?
(A) Elective lymph node dissection and amputation at the metacarpophalangeal joint
(B) Elective lymph node dissection and nail ablation
(C) Sentinel node biopsy and amputation at the level of the interphalangeal joint
(D) Sentinel node biopsy and excision of skin with 1-cm margins
(E) Sentinel node biopsy and ray amputation of the carpometacarpal joint
The correct response is Option C.
The annual incidence of melanoma has increased significantly from a lifetime risk of 1:1500 in 1900 to the current risk of 1:35. Nail apparatus melanomas, and specifically subungual melanomas, pose a difficult problem because they are often diagnosed late. Late diagnosis correlates with thicker melanomas and greater risk of metastasis. Approximately 20% to 25% of subungual melanomas may be amelanotic. Sentinel node biopsy has become the standard of care, and since its advent, elective lymph node dissection is no longer recommended.
Because of the proximity of the nail matrix to the periosteum and bone, adequate resection margins are not achieved with standard wide excision of 1 to 2 cm, and recommendation for excision is at the distal interphalangeal joint of the finger or interphalangeal joint of the thumb. Melanoma can track along the neurovascular bundles. Amputation at a more proximal level is not needed and does not improve prognosis. More proximal amputation also results in a critical loss of function, particularly concerning the thumb.
The presence of pigment in the paronychial area (Hutchinson sign) is shown in the photograph. An area of pigmentation in the eponychium is almost pathognomonic for subungual malignant melanoma.
A 70-year-old man is referred for evaluation of a 2.2 x 1.3-cm pigmented lesion on the right side of the neck over the midsection of the sternocleidomastoid muscle. Punch biopsy shows lentigo maligna melanoma with a Breslow thickness of 0.6 mm. Wide surgical excision with a 1-cm margin is performed. A photograph is shown above. The specimen report upgrades the Breslow thickness to 1.2 mm. Further evaluation, including CT scan of the head, neck, chest, and abdomen, shows no associated metastases. Which of the following represents the amount of additional margin of excision that is needed for adequate local management of this lesion?
(A) No additional margin is necessary
(B) 0.5 cm
(C) 2 cm
(D) 3 cm
(E) 5 cm
The correct response is Option A.
Breslow thickness measured from the top of the granular layer to the deepest level of tumor is the single most important factor in the prognosis of melanoma. Sampling error failing to reveal the deepest point of a lesion during incisional biopsy techniques is quite common, even in experienced hands. This leads to possible need for reexcision and sometimes lymph node management. The punch biopsy either picked up a thinner area or did not include the full thickness of skin. Because of the surface extent of the lesion, a punch biopsy is still appropriate as the initial diagnostic method; however, when the entire lesion is analyzed, the thicker areas may be revealed and call into question the adequacy of the original margin of excision. In this case, no additional margin is necessary. A study performed by the World Health Organization has shown that for melanomas less than 2 mm, a surgical margin of 1 cm is just as effective as a 3-cm margin, and there is no difference in locoregional recurrence, in-transit metastases, or five-year survival rates.
Current practice recommendations advise a margin of excision of 0.5 to 1 cm for in situ melanoma. Invasive lesions with a Breslow thickness between 0 and 1 mm should have a 1-cm margin of excision. For lesions between 1 and 2 mm, a 1- to 2-cm margin is acceptable, using closer to 2 cm when the anatomic area is more forgiving, such as the trunk, or when the thickness is closer to 2 mm. Lesions between 2.1 and 4 mm should have a 2-cm margin. For lesions thicker than 4 mm, a margin of at least 2 cm should be used, but a 3-cm margin should be considered if ulceration of the tumor is present.
