Prevalence: accounts for about 10-15% of all cases of melanoma.
Incidence: more frequent in males than females, with a ratio of 2:1. Nodular melanomas occur most often in the fifth or sixth decade.
Site: Nodular melanomas affect any area of skin, but are more often found on the extremities.
Course: Nodular melanoma lesions appear and evolve over months and tend to extend vertically in the skin.
Appearance: Nodular melanoma is most commonly dark brown, red-brown, or red-black and is dome-shaped, polypoid, or pedunculated. It is occasionally amelanotic or flesh colored and resembles flesh-colored dermal nevi or basal cell carcinoma. These amelanotic melanomas represent 2% of all melanomas. Lesions eventually erode, ulcerate and bleed.
Differential diagnosis: Hemangioma which is compressible with its color density changed with firm finger pressure.
Monday, July 21, 2008
What is Nodular melanoma
Sunday, July 20, 2008
What is Superficial Spreading Melanoma
Prevalence: the most common subtype of melanoma, accounting for 70-80% of all cases.
Incidence: most common in middle age, from the fourth to fifth decade, slightly more common in females than males and usually affects Caucasians.
Anatomic site: Any area of the skin may be affected but they are most often found on the upper back of both men and women and on the legs of women.
Clinical appearance: Superficial Spreading Melanoma lesions tend to be greater than 6 mm in diameter, flat and asymmetric with varying colors.
Specific features: The hallmark of Superficial Spreading Melanoma is the haphazard combination of many colors, but it may be uniformly brown or black. Colors may become more diverse as time proceeds. A dull red color is frequently observed, which may occupy a small area or may dominate the lesion.
Course: Superficial Spreading Melanoma begins in a pre-existing lesion, in a nonspecific manner and then changes shape by radial spread and regression.
The radial growth phase (lateral spread of lesions within the skin): may last for months or for years, before nodules develop. The random migration of cells, along with the process of regression, results in lesions with an endless variety of shapes and sizes. The shape is bizarre if left untreated for years.
Wednesday, May 28, 2008
Atypical Mole (Dysplastic Nevus) Syndrome
Cutaneous melanoma may occur as isolated, so-called sporadic cases; in association with multiple atypical nevi; or in familial clusters, in which case it is referred to as the atypical-mole syndrome (AMS), formerly known as dysplastic nevus syndrome. In the late 1970s, the dysplastic nevus (DN) or atypical mole (AM) was identified in melanoma-prone families. It was then determined that AMs are cutaneous markers that identify specific family members who are at increased risk for melanoma. The AM may also be the single most important precursor lesion of melanoma. These nevi may occur in persons from melanoma-prone families and in persons who lack both a family history and a personal history of melanoma.
Atypical-mole syndrome and familial melanoma.
Numerous families with multiple melanoma patients have been reported. These patients usually develop melanoma at a young age, have a predisposition to multiple primary melanomas, and have the tendency to develop thin, superficial-spreading melanomas. Large, unusual-looking moles were initially recognized as a precursor to melanoma in patients with familial cutaneous melanoma. This syndrome was named B-K mole syndrome from two of the probands, and the precursor nevi were designated as B-K moles and later referred to as dysplastic nevi. The syndrome is now called the atypical-mole syndrome. Recent estimates suggest that approximately 32,000 persons in the
One study showed that the hereditary cutaneous malignant melanoma/atypical-mole syndrome does not predispose to other cancers.
The National Institutes of Health (NIH) Consensus Conference on Diagnosis and Treatment of Early Melanoma has defined the familial atypical mole and melanoma syndrome as (1) the occurrence of malignant melanoma in one or more first- or second-degree relatives; (2) a large number of melanocytic nevi (MN), often more than 50, some of which are atypical and often variable in size; and (3) melanocytic nevi that demonstrate certain histologic features. AMS probably represents a spectrum. At one end all members of a kindred have AMs and some have malignant melanoma (MM). At the other end are persons with one AM without a personal and/or family history of MM.
Patients with AMS, familial or sporadic, are at significant risk for developing melanoma. Atypical moles have been observed in 8% of patients with nonfamilial (sporadic) melanoma, and the transformation into superficial-spreading melanoma has been photographically documented. Family members without atypical moles do not show any apparent increase in melanoma risk. The frequency of sporadic AMs in the general population is unknown.
Atypical moles are found on the skin of 90% of patients with hereditary melanomas, and more than 50% of melanomas in this group are associated histologically with and probably evolve from atypical moles. The lifetime risk of developing cutaneous melanoma among the white population in the
Among atypical-mole-bearing family members, those patients with melanoma have very large numbers of nevi more frequently than patients with AMs without melanoma. Family members with AMs have more nevi than do patients who have only common acquired nevi.
Morphology.
These unusual nevi differ in a number of important ways from typical acquired pigmented nevi or moles. Atypical moles are larger than common moles. They have a mixture of colors, including tan, brown, pink, and black. The border is irregular and indistinct and often fades into the surrounding skin. The surface is complex and variable, with both macular and papular components. A characteristic presentation is a pigmented papule surrounded by a macular collar of pigmentation ("fried-egg lesion"). In one study, the total number of nevi and macular components were the only useful features to predict histologic melanocytic dysplasia. However, "fried-egg lesions" often do not display histologic melanocytic dysplasia. In contrast, the absence of a macular component in melanocytic nevi in a person with fewer than 13 total body nevi accurately predicts the absence of melanocytic dysplasia on histologic examination.
Development and distribution.
Atypical moles are not present at birth, but begin to appear in the mid-childhood years as typical common moles. The appearance changes at puberty, and newer lesions continue to appear well after the age of 40. Common moles occur most often on sun-exposed areas. AMs occur in those locations and at unusual sites such as the scalp, buttocks, and breast. The predilection sites for melanoma in familial AMS patients of both sexes correspond with the distribution of nevi; in males nevi and melanoma counts are higher on the back, in females both the back and the lower extremities are affected. These findings strongly suggest an association between nevus distribution and melanoma occurrence and site in familial AMS.
Histology.
The NIH Consensus Conference listed the histologic criteria as follows: architectural disorder with asymmetry, subepidermal (concentric eosinophilic and/or lamellar) fibroplasia, and lentiginous melanocytic hyperplasia with spindle or epithelioid melanocytes aggregating in nests of variable size and forming bridges between
adjacent rete ridges. Melanocytic atypia may be present to a variable degree. In addition, there may be dermal infiltration with lymphocytes, as well as the "shoulder" phenomenon (intraepidermal melanocytes extending singly or in nests beyond the main dermal component).
Friday, May 23, 2008
What are Nevi, or Moles, part three
SPECIAL FORMS
Special forms of pigmented lesions include congenital nevus, halo nevus, nevus spilus, Becker's nevus, benign juvenile melanoma (Spitz nevus), blue nevus, and labial melanotic macules.
Congenital nevi.
Congenital nevi (birthmarks) are present at birth and vary in size from a few millimeters to several centimeters, covering wide areas of the trunk, an extremity, or the face. Not all pigmented lesions present at birth are congenital nevi; cafe-au-lait spots may also be present at birth. The largest lesions are referred to as giant hairy nevi. Giant congenital nevi on the trunk are referred to as bathing trunk nevi .
Congenital nevi may contain hair; if present, it is usually coarse. Such nevi are uniformly pigmented, with various shades of brown or black predominating , but red or pink may be a minor or sometimes predominant color . Most are flat at birth, but become thicker during childhood, and the surface becomes verrucous and sometimes nodular.
The risk of developing melanoma in very large lesions is significant. Malignant transformation may occur early in childhood; therefore, large, thick lesions should be removed as soon as possible. The risk of developing malignancy may be related to the number of melanocytes and consequently to the size and thickness; however, melanomas have also developed in small congenital nevi. There is a large risk of melanoma in patients with nevi covering more than 5% of the body surface area. The risk of malignant degeneration for smaller congenital nevi is unknown. A report showed histologic features of congenital nevi in 8.1% of the melanoma specimens studied.
Management.
The incidence of melanomas in small congenital nevi is unknown. Persons with large congenital nevi (bathing trunk nevi) are at definite risk for the development of melanoma in childhood, and these nevi are managed by a plastic surgeon. Because of the possibility of malignant degeneration of congenital nevi, some experts recommend that all congenital nevi be considered for prophylactic excision. All congenital moles should be checked by a dermatologist. If a congenital mole is not surgically removed, it should be examined on a regular basis.
Nevus spilus.
Nevus spilus is a hairless, oval or irregularly shaped, brown lesion that is dotted with darker brown-to-black spots. The brown area is usually flat, and the black dots may be slightly elevated and contain typical nevus cells . There is considerable variation in size, ranging from 1 to 20 cm; they may appear at any age. The anatomic position or time of onset is not related to sun exposure.
Nevus spilus is flat and necessitates excision and closure if the patient desires removal.
Becker's nevus.
Becker's nevus is not a nevocellular nevus because it lacks nevus cells. The lesion is a developmental anomaly consisting of either a brown macule , a patch of hair, or both . Nonhairy lesions may later develop hair. The lesions appear in adolescent men on the shoulder, submammary area, and upper and lower back. Becker's nevus varies in size and may enlarge to cover the entire upper arm or shoulder. The border is irregular and sharply demarcated. Malignancy has never been reported.
Becker's nevus is usually too large to remove and is best left untouched. The hair may be shaved or permanently removed.
Halo nevi.
A compound or dermal nevus that develops a white border is called a halo nevus. The depigmented halo is symmetric and round or oval with a sharply demarcated border . There are no melanocytes in the halo area. Histologically, chronic inflammatory cells may be present. Most halo nevi are located on the trunk; they never occur on palms and soles. Halo nevi develop spontaneously, most commonly during adolescence. They may occur as an isolated phenomenon or several nevi may spontaneously develop halos. Halos may repigment with time or the nevus may disappear. Repigmentation does not follow removal of the nevus. The incidence of vitiligo may be increased in patients with halo nevi. A halo may rarely develop around malignant melanoma, but in such instances it is usually not symmetric.
Removal of a halo nevus is unnecessary unless the nevus has atypical features. Parental concern over this impressive change is often reason for a conservative excision. In such cases, the mole part of a halo nevus may be removed by shave or excision.
Spitz nevus.
Spitz nevus, or benign juvenile melanoma, is most common in children, but does appear in adults. The term melanoma is used because the clinical and histologic appearance is similar to melanoma. They are hairless, red or reddish-brown, dome-shaped papules or nodules with a smooth or warty surface; they vary in size from 0.3 to 1.5 cm. The color is caused by increased vascularity, and bleeding sometimes follows trauma. Spitz nevi are usually solitary but may be multiple. They appear suddenly and, contrary to slowly evolving common moles, patients can sometimes date their onset. The benign juvenile melanoma should be removed for microscopic examination. Histologic differentiation from melanoma is sometimes difficult.
Blue nevus.
The blue nevus is a slightly elevated, round, regular nevus, usually less than 0.5 cm, and contains large amounts of pigment located in the dermis . The brown pigment absorbs the longer wavelengths of light and scatters blue light (Tyndall effect). The blue nevus appears in childhood and is most common on the extremities and dorsum of the hands. A rare variant, the cellular blue nevus, is larger (usually greater than 1 cm) and nodular and is frequently located on the buttock. There are reported cases of malignant degeneration of these larger blue nevi into melanomas.
Labial melanotic macule.
Brown macules on the lower lip are relatively common, especially in young adult women. Histologically, they resemble freckles and not lentigo, but unlike freckles, they do not darken with sun exposure.
What are Nevi, or Moles, part two
Junction nevi.
Junction nevi are flat (macular) or slightly elevated, and they are light brown to brown-black with uniform pigmentation that may be slightly irregular . The surface is smooth and flat to slightly elevated, and the border is round or oval and symmetric. Most lesions are hairless. Junction nevi vary in size from 0.1 to 0.6 cm; some are larger. Junction nevi may change into compound nevi after childhood, but they remain as junction nevi on palms, soles, and genitalia. Junction nevi are rare at birth and generally develop after the age of 2 years. Degeneration into melanoma is very rare.
Compound nevi.
Compound nevi are slightly elevated and flesh colored or brown. They are elevated and smooth or warty and become more elevated with increasing age . They are uniformly round, oval, and symmetric. Hair may be present. If a white halo appears at the periphery of the lesion, it is referred to as a halo nevus.
Dermal nevi.
Dermal nevi are brown or black, but may become lighter or flesh-colored with age. Lesions vary in size from a few millimeters to a centimeter. The variety of shapes reflects the evolutionary process in which moles extend downward with age and nevus cells degenerate and become replaced by fat and fibrous tissue.
Dome-shaped lesions are the most common . They generally appear on the face and are symmetric, with a smooth surface. They may be white or translucent, with telangiectatic vessels on the surface mimicking basal cell carcinoma. The structure may be warty or polypoid . Pedunculated lesions with a narrow stalk are located on the trunk, neck, axilla, and groin. They may appear as a soft, flabby, wrinkled sack.
Elevated nevi are exposed and are prone to trauma from clothing and other stimuli, often causing them to bleed and inflame, influencing some patients to suspect malignancy. White borders may appear, creating a halo nevus. Degeneration to melanoma is very rare, but dermal nevi may resemble nodular melanoma; therefore, knowledge of duration is important.
Management of common moles
Suspicious lesions.
Any pigmented lesion suspected of being malignant should be biopsied or referred for a second opinion. Suspicious lesions should be completely removed by excisional biopsy down to and including subcutaneous tissue.
Nevi.
Patients frequently request removal of nevi for cosmetic purposes. It is good practice to biopsy all pigmented lesions; therefore, total removal by electrocautery should be avoided. Nevi are removed either by shave excision or by simple excision and closure with sutures. Most common nevi are small and consequently shave excision is adequate.
Recurrent previously excised nevi (pseudomelanoma).
Weeks to months after incomplete removal of a nevus, brown macular pigmentation may appear in the scar. Some nevus cells remain with shave excision and partial repigmentation is possible. Residual pigmentation may be removed with electrocautery or cryosurgery. An unusual histologic picture resembling melanoma (pseudomelanoma) may follow partial removal of nevi. If the repigmented area is excised, the pathologist should always be notified that the submitted tissue was acquired from a previously treated area. Histologically, the melanocytes appear atypical but are confined to the epidermis, and there is no lateral spread of individual melanocytes.
Nevi with small dark spots.
A small percentage of small dark dots within melanocytic nevi is due to melanoma. These roundish areas of brown or black hyperpigmentation measure 3 mm or less in diameter and are located peripherally. Biopsy specimens of nevi with small dark dots should be sectioned to ensure histologic examination of this focus of hyperpigmentation.
Tuesday, May 20, 2008
What are Nevi, or Moles
Nevi, or moles, are benign tumors composed of nevus cells that are derived from melanocytes. The well-publicized increase in the incidence of melanoma has stimulated the layperson's interest and concern about pigmented lesions.
Many myths surround moles; for example, that hairs should not be plucked from moles or that moles should not be removed or disturbed. These myths should be clarified.
Nevus cells.
The nevus cell differs from melanocytes in a number of ways. The nevus cell is larger, lacks dendrites, has more abundant cytoplasm, and contains coarse granules. Nevus cells aggregate in groups (nests) or proliferate in a nonnested pattern in the basal region at the dermoepidermal junction. Nevus cells in the dermis are classified into types A (epithelioid), B (lymphocytoid), and C (neuroid). Through a process of maturation and downward migration, type A epidermal nevus cells develop into type B cells and then into type C dermal nevus cells.
Incidence and evolution.
Moles are so common that they appear on virtually every person. They are present in 1% of newborns and increase in incidence throughout infancy and childhood, reaching a peak at puberty. Size and pigmentation may increase at puberty and during pregnancy. A few may continue to appear throughout life. Nevi may occur anywhere on the cutaneous surface. There is a strong correlation between sun exposure and the number of nevi. Acquired nevi on the buttock or female breast are unusual.
Nevi vs. melanoma.
Nevi exist in a variety of characteristic forms that must be readily recognized to distinguish them from malignant melanoma. Except for certain types, such as large congenital nevi and atypical moles, most nevi have a very low malignant potential.
Nevi vary in size, shape, surface characteristics, and color. The important fact to remember is that each individual nevus tends to remain uniform in color and shape. Although various shades of brown and black may be present in a single lesion, the colors are distributed over the surface in a uniform pattern.
Melanomas consist of malignant pigment cells that grow and extend with little constraint through the epidermis and into the dermis. Such unrestricted growth produces a lesion with a haphazard or disorganized appearance, which varies in shape, color, and surface characteristics. Nevertheless, the characteristics of uniformity cannot always be relied on to differentiate benign from malignant lesions because very early melanomas may appear quite uniform, having a round or oval shape with a uniform brown color.
Examination with a hand lens.
Careful inspection of suspicious lesions with a powerful hand lens may reveal irregularities in the border or minute areas of regression that suggest malignancy. Dome-shaped, pigmented lesions with uniform speckling over the surface are usually benign dermal nevi . A flat, dark macule with a uniform, netlike pattern is usually a lentigo. Lentigines with netlike patterns are most often found on the trunk.
COMMON MOLES
Nevi may be classified as acquired or congenital, but clinical classification is based on appearance.
Classification.
Common moles are subdivided into three types: junctional, compound, and dermal, based on the location of the nevus cells in the skin. The three types represent sequential developmental stages in the life history of a mole. During childhood, nevi begin as flat junction nevi in which the nevus cells are located at the dermoepidermal junction. They evolve into compound nevi when some of the cells migrate into the dermis. Migration of all of the nevus cells into the dermis results in a dermal nevus. Dermal nevi usually form only in adults, but this evolution does not consistently occur. Nevi with cells confined to the dermoepidermal junction area tend to be flat, whereas those with cells confined to the dermis are usually elevated.
Friday, May 16, 2008
Melanoma Staging System, TNM Definitions
PRIMARY TUMOR
TX: Cannot be assessed (shave biopsy, regressed lesion)
T0: Unknown primary
Tis: In situ melanoma
T1: -1.0 mm Breslow thickness
a. without ulceration
b. with ulceration or Clark level IV or V
T2: 1.01 to 2.0 mm
a. without ulceration
b. with ulceration
T3: 2.01 to 4.0 mm
a. without ulceration
b. with ulceration
T4: more than 4.0 mm
a. without ulceration
b. with ulceration
REGIONAL LYMPH NODE INVOLVEMENT
NX: Cannot be assessed (previously removed)
N0: No regional node metastasis
N1: Metastasis in one regional node
a. micrometastasis (diagnosed by SLNB or elective lymph node dissection)
b. macrometastasis (clinically palpable or found on imaging studies, confirmed histologically, or gross extracapsular extension)
N2: Metastasis in two to three regional nodes
a. micrometastasis
b. macrometastasis
c. in-transit or satellite metastasis without nodal metastasis
N3: Metastasis to regional nodes, matted nodes, or in-transit or satellite metastasis with positive metastatic nodes
DISTANT METASTASIS
MX: Cannot be assessed
M0: No distant metastasis
M1a: Distant skin, subcutaneous, or lymph node metastasis with normal LDH
M1b: Lung metastasis with normal LDH
M1c: All other distant metastasis or any distant site with elevated LDH
Friday, March 28, 2008
Skin cancer facts: Malignant Melanoma
Skin cancer ---> Melanoma skin cancer
Skin Cancers are the most commonly diagnosed malignant tumors in the United States, with an incidence of approximately 1.4 million new cases annually. Basal cell and squamous cell skin carcinoma account for 96% of new non melanoma skin cancers. Malignant Melanoma accounts for 4% of skin cancers.
Risk factors for development of skin melanoma include ultraviolet light (UVL) exposure, fair complexion/inability to tan, blue or green eyes, blonde or red hair, freckling, history of actinic keratosis or non melanoma skin cancer, history of blistering or peeling sunburns, immunosuppression, personal or family history of melanoma, CDKN2A/p16/MC1R mutation, xeroderma pigmentosa, atypical (dysplastic) nevus, more than 100 normal nevi, and giant congenital melanocytic nevus.
The ABCD rule is used to assess skin lesions for melanoma risk: A is for asymmetry; B is border irregularity; C is color, and D is diameter greater than 6 mm.
Melanoma prognosis is inverse correlated to tumor thickness; ulceration and increased mitotic rate are independent survival risk factors; nodal tumor burden (uninvoled versus microscopic versus macroscopic disease) has an inverse correlation with survival.
Treatment: For melanoma in situ, excision margins of 0.5 to 1 cm are indicated; for invasive melanoma, wide excision of the primary tumor with margins generally ranging from 1 to 2 cm is indicated for local control.
Clinically involved lymph nodes should be resected; patients with primary melanomas of 1 mm thickness or greater and clinically negative nodes should be considered for sentinal lymph node biopsy.
Thursday, March 27, 2008
Malignant melanoma
Skin cancer ---> Melanoma skin cancer
Melanoma arises from malignant proliferation of melanocytes.
Epidemiology
The incidence of and mortality from melanoma are increasing. Its incidence is approximately 10 per 100 000 per year. The highest incidence occurs in white-skinned individuals in Australia and New Zealand. Melanoma is more common in women than in men.
Pathology
Ultraviolet exposure is a major etiological factor, particularly short, intense exposure resulting in sunburn during childhood. Phenotypic factors associated with melanoma include fair skin, red or blonde hair, blue eyes, inability to tan, freckles, lentigines, large numbers of benign melanocytic nevi and the presence of dysplastic nevi.
Important risk factors for malignant melanoma
Presence of precursor lesions (dysplastic melanocytic nevi)
Family history of melanoma in parents or siblings
Skin phototypes I and II with an inability to tan
Excess sun exposure, especially during childhood
Clinical features
Malignant melanoma has two patterns of growth, radial and vertical. Radial growth is horizontal within the epidermis and superficial dermal layers, as in the lentigo maligna, acral/mucosal lentiginous and superficial spreading types. During this stage of growth the tumor does not have the capacity to metastasize. Vertical growth occurs with time, and the melanoma grows downwards into the deeper dermal layers as an expansile mass, lacking cellular maturation. This correlates with the emergence of a clone of cells with metastatic potential. The nature and extent of this vertical growth phase determine the biological behavior of malignant melanoma. The different types of malignant melanoma are categorized on morphology and histological findings.
Superficial spreading
Superficial spreading is the most common variant of melanoma (70%), presenting as a macule or papule, usually greater than 0.5 cm in diameter. There is variable pigmentation (from pale brown to blue-black), an irregular edge, and surface oozing or crusting. In males it most frequently presents on the back, while in females the leg is the most common site. In the radial growth phase it is characterized by atypical melanocytes, singly and in clusters, widely scattered throughout the layers of the epidermis. Left untreated it may progress to the vertical growth phase over months to years.
Nodular melanoma
Nodular melanoma is the second most common variant (14%) and, by definition, presents in the vertical growth phase. It classically presents as a rapidly enlarging, frequently ulcerated, blue-black nodule.
Lentigo maligna
Lentigo maligna presents as an irregularly pigmented macule, slowly enlarging over many years, commonly on the cheek or temple of an elderly person. It is characterized by basally located atypical melanocytes. Development of a more rapidly growing, deeply pigmented papule or nodule indicates dermal invasion by malignant melanocytes (lentigo maligna melanoma).
Acral lentiginous melanoma
Acral lentiginous melanoma is an uncommon subtype, although it is the predominant variant in the Afro-Caribbean population. The sole of the foot is most often affected and lesions may also arise on the digits. Subungual or periungual melanoma, a variant of acral lentiginous melanoma, occurs either as a linear pigmented streak in the nail or an isolated nail dystrophy, accompanied by the pigmentation of the proximal nail fold (Hutchinson's sign).
Amelanotic melanoma
Amelanotic melanoma is a non-pigmented variant of melanoma.
Malignant melanoma on mucous membranes
Malignant melanoma on mucous membranes is very rare and may affect the vulva, urethra and anus. It has a poor prognosis, due in part to its often advanced stage at presentation.
Investigations
Skin biopsy
An excision skin biopsy must be performed to confirm the diagnosis. This will give important histological data and provide valuable staging information.
Management
The management of malignant melanoma varies according to the stage at presentation, and ranges from surgical excision to radiotherapy and chemotherapy.
Prognosis
Melanoma has a mortality rate of 25% and therefore early diagnosis and treatment is essential. Prognostic factors include thickness, level of invasion, gender and site of tumor.
Histological data from melanoma
Clarke's level
I melanoma cells confined to epidermis
II melanoma cells invade papillary dermis
III melanoma cells completely occupy papillary dermis
IV melanoma cells invade mid-reticular dermis
V melanoma cells invade subcutaneous fat
Tumor thickness in mm from granular layer of the epidermis to maximum depth (Breslow thickness)
Presence of radial or vertical growth
Tumor infiltrating lymphocytes
Mitoses per mm2
Presence or absence of tumor regression (mitosis, inflammatory infiltrate, pigmentary incontinence, fibrosis and dermal scarring, and vascular proliferation)
Microsatellites
Evidence of perineural infiltrate
Evidence of vascular and lymphatic invasion
Whether excision is complete
TNM staging system for melanoma
Stage (T) Primary tumor Lymph node (N) Distant metastases (M)
0 In situ tumors No nodes No Distant metastases (M)
IA -1mm, IIB 2.01-4 mm with ulceration No nodes No Distant metastases (M)
>4 mm, no ulceration No nodes No Distant metastases (M)
IIC >4 mm with ulceration No nodes No Distant metastases (M)
IIIA Any Breslow thickness, no ulceration Micrometastases in nodes No Distant metastases (M)
IIIB Any Breslow thickness with ulceration Micrometastases in nodes No Distant metastases (M)
Any Breslow thickness, no ulceration Up to 3 palpable nodes No Distant metastases (M)
Any Breslow thickness ± ulceration No nodes but in-transit metastases or satellites None
IIIC Any Breslow thickness with ulceration Up to 3 palpable nodes No Distant metastases (M)
Any Breslow thickness ± ulceration 4 or more palpable nodes or matted nodes or in-transit metastases with nodes No Distant metastases (M)
IV M1: skin, subcutaneous or distant lymph nodes
M2: lung
M3: all other sites or any site with raised lactate dehydrogenase
Wednesday, March 26, 2008
Skin Mole or Nevus
Melanoma skin cancer ---> Pre skin cancer ---> skin cancer moles
Lentigo
A lentigo is a common lesion that presents as a small, pigmented macule due to an increase in the number of melanocytes within the basal layer of the epidermis. These are unaffected by sunlight. Solar lentigines develop on sun-exposed sites following either acute severe sunburn in young adults or chronic ultraviolet exposure in the elderly. Multiple lentigines may rarely be a manifestation of Peutz-Jeghers syndrome, particularly when distributed on the lips, buccal mucosa and acral sites.
Acquired melanocytic nevi
Acquired melanocytic nevi are common benign proliferations of melanocytes. They can be classified according to the site of the cluster of melanocytes. Junctional nevi describe the position of the cells at the dermal-epidermal junction above the basement membrane. Intradermal nevi describe cells that are exclusively in the dermis. Compound nevi have histological features of both junctional and intradermal nevi.
Junctional nevi present as small, dark brown, evenly pigmented, symmetrical macules. The majority of naevi in children are junctional and occur on any body site. Compound nevi (where melanocytes are present in both the epidermis and dermis) occur at any site and vary from light brown papules to dark brown papillomatous plaques. Intradermal nevi are usually detected in the third decade, frequently on the face, and may be devoid of pigment. They may be dome-shaped or pedunculated skin tags. These lesions appear in early childhood and reach a maximum in young adulthood. There is then a gradual involution, and most lesions disappear by the age of 60. A skin biopsy is only required when clinical differentiation from malignant melanoma is difficult.
Blue nevus
A blue nevus is an acquired, benign, firm, dark blue to black, sharply defined papule representing a deep dermal aggregate of melanocytes. The dermal melanocytes are thought to represent melanocytes which have failed to migrate from the neural crest to the epidermis during fetal life. Blue nevus is most common on the dorsum of hands or feet of older children and young adults. Malignant change is very rare.
Spitz nevus
A Spitz nevus is a benign melanocytic tumor that is distinct from acquired melanocytic nevi on both clinical and pathological grounds. The majority occur in children as a discrete, red-brown or pink papule on the face. The clinical presentation is distinctive and there is often a history of recent rapid growth. Differentiation from malignant melanoma may be difficult and in these cases complete excision is recommended.
Mongolian spot
A Mongolian spot is a congenital grey-blue macular lesion that can occur anywhere on the skin but is characteristically located on the lumbo-sacral area. Histologically there are ectopic melanocytes in the dermis, possibly interrupted in their migration from the neural crest to the epidermis. Mongolian spots disappear in early childhood. No melanomas have been reported in these lesions.
Nevus spilus
A nevus spilus is a common lesion consisting of a light brown macule, varying in size from a few centimeters to a very large area, with many darker small macules (2-3 mm) or papules scattered throughout. Histologically, the background macule shows an increased number of melanocytes and the scattered lesions are either junctional or compound nevi. Malignant melanoma very rarely arises in these lesions.
Dysplastic melanocytic nevus
Dysplastic melanocytic nevi are melanocytic lesions with atypical clinical and histological features. They are regarded as potential precursors of superficial spreading melanoma and also as markers of persons at risk for developing primary malignant melanoma. These pigmented lesions are clinically distinct from acquired melanocytic nevi, being larger and more variegated in color, with an asymmetrical outline and irregular border. Lesions may occur sporadically or may arise against a background of dysplastic nevus syndrome, an autosomal dominant condition with multiple atypical nevi. Surgical excision of lesions with minimal margins is recommended, especially in lesions that are changing or those that cannot be closely followed by the patient (on the scalp or back).
CLINICAL ALERT
Six signs of malignant melanoma
A
Asymmetry in shape
B
Border is irregular
C
Color variation-shades of brown, black, grey, red and white
D
Diameter is usually large, >6 mm
E
Elevation is almost always present
Tuesday, March 25, 2008
Causes of Melanoma
Melanoma skin cancer ---> Causes of melanoma
Numerous environmental and genetic risk factors have been implicated in the development of cutaneous melanoma. Risk factors include ultraviolet light (UVL) exposure, fair complexion/inability to tan, blue or green eyes, blonde or red hair, freckling, history of actinic keratosis or nonmelanoma skin cancer, history of blistering or peeling sunburns, immunosuppression, personal or family history of melanoma, xeroderma pigmentosa, atypical (dysplastic) nevus, more than 100 normal nevi, and giant congenital melanocytic nevus. Patients with a significant history of sun exposure are at particularly high risk, especially if they experienced peeling or blistering sunburns, even during childhood. Melanoma occurs infrequently in skin of color, suggesting that skin pigment plays a protective role. Melanoma incidence is subject to large geographic and ethnic variations, mainly because of an inverse correlation with latitude and with degree of skin pigmentation. Populations residing closer to the equator have a higher incidence of melanoma. Certainly UVL exposure from sun or artificial light sources is considered the best-known risk factor. However, UVL exposure does not cause all or even most melanomas.
Adults with more than 100 clinically normal-appearing nevi, children with more than 50 clinically normal-appearing nevi, and any patient with atypical or dysplastic nevi are at risk. A prior history of melanoma places a patient at increased risk, with 5% to 10% of individuals developing a second primary melanoma. This risk of developing a second primary is lifelong and can occur anywhere on the skin. Therefore, long-term surveillance with a thorough total body examination is recommended.
A genetic component has been implicated in the pathogenesis of melanoma. Of patients with melanoma, 10% to 15% report a positive family history. The genetic etiology of melanoma represents an area of future discovery.
The hereditary nature of cutaneous melanoma was also noted in the 1970s. Members afflicted with the B-K mole syndrome, named after two families, acquired large, irregular, and dysplastic nevi, often in sun-protected regions of the body such as the scalp and trunk. Familial association of melanoma among individuals with atypical nevi, is termed Familial Atypical Multiple Mole-Melanoma Syndrome, or FAMMM syndrome, with an autosomal dominant inheritance pattern. An atypical nevus is not a pre melanoma but represents a genetic marker for increased risk of development of melanoma, which may occur anywhere on the skin surface including sun-protected sites. In fact more than 50% to 75% of melanomas develop on clinically normal skin de novo, not in preexisting melanocytic lesions.
Xeroderma pigmentosa (XP) is a rare autosomal recessive disorder associated with a reduced or absent ability to repair DNA damaged by ultraviolet light. Consequently, this disorder results in the development of multiple primary cutaneous malignancies, including melanoma as well as BCC and SCC. Individuals are usually diagnosed with their first cancer before the age of 10 years. Unfortunately, the development of skin cancers is relentless.
Congenital melanocytic nevi (CMN) are present at birth or appear within the first 6 months of infancy. An estimated 1% to 6% of children are born with CMN. The nevi are classified by size. Small CMN measure less than 1.5 cm in diameter and account for the majority of lesions. Medium CMN measure between 1.5 and 19.9 cm in diameter. Large CMN, also termed giant congenital nevi, measure 20 cm or greater. This large size can lead to significant cosmetic and psychosocial implications. The risk of melanoma development in small and medium-size CMN is similar to any other area of skin. Melanoma development in small and medium CMN usually occurs after childhood and arises from the dermoepidermal junction, making early detection feasible. Routine prophylactic removal of small and medium CMN is rarely indicated in the absence of signs or symptoms for malignant progression. Conversely, giant congenital nevi carry an increased risk for melanoma, with an estimated rate of 5% to 20%. Of giant congenital nevi that progress to melanoma, 70% are diagnosed prior to age 10 years. Melanoma can originate deep in the epidermis in giant congenital nevi. Consequently, diagnosis within the setting of giant congenital nevi is challenging and may develop deep in the skin with a more advanced primary lesion.
Monday, March 24, 2008
Metastatic Workup for Melanoma
Melanoma skin cancer ---> metastatic melanoma ---> diagnosis of melanoma
In an attempt to standardize staging workup for melanoma, the National Comprehensive Cancer Network (NCCN) has published guidelines. There are three basic reasons to perform a metastatic workup following the diagnosis of primary cutaneous melanoma: (a) for staging and prognosis, (b) to detect an early metastasis with potential survival benefit, and (c) to avoid morbidity of an extensive surgical procedure by detection of a distant metastasis. The best test for the staging workup still starts with a history (focused review of systems concentrating on constitutional, respiratory, neurologic, hepatic, musculoskeletal, gastrointestinal, skin, and lymphatic systems) and physical examination (total body skin examination, palpation of lymph nodes). Routine imaging and blood studies in asymptomatic patients are low in both sensitivity and specificity. False-positive staging tests are common and lead to more tests and patient distress. SLNB represents the best baseline staging test, with both relatively high sensitivity and specificity in patients at significant risk for metastasis. The ability to detect stage IV disease with routine studies is small if the SLNB is negative. Ultrasound is perhaps the most sensitive noninvasive test to detect small nodal metastases. However, the sensitivity and specificity of ultrasound and PET scanning are inferior to tissue diagnosis with SLNB.
Evaluation for Metastatic Melanoma
Melanoma skin cancer ---> metastatic melanoma ---> diagnosis of melanoma
The follow-up evaluation for patients with AJCC stage I, II, or III melanoma who are rendered tumor free by surgery should include regular histories and physical examinations. The use of extensive and frequent radiographic studies and blood work in asymptomatic, clinically disease-free patients is rarely productive. In 2004, the National Comprehensive Cancer Network issued guidelines for follow-up of patients with various stages of disease. For AJCC stage IA, patients should undergo a history and physical examination with emphasis on skin and nodal examinations every 3 to 12 months as clinically indicated. For AJCC stage IB to III, patients should undergo a history and physical examination every 3 to 6 months for 3 years, then every 4 to 12 months for 2 years, then annually as clinically indicated. The use of chest radiographs and blood work, and other imaging scans are indicated when clinically indicated, is based on the history and physical examination.
Melanoma can disseminate to any organ. The most common sites of recurrence are skin, subcutaneous tissues, and distant lymph nodes, followed by visceral sites. Common visceral sites of metastasis, in order of decreasing occurrence, are lung, liver, brain, bone, and gastrointestinal tract. Most patients who die with disseminated disease have multiple organ involvement. Frequently, the cause of death is respiratory failure or brain complications. Patients with disseminated disease have a poor prognosis, with a mean survival of approximately 6 months. Cure with any treatment is rare. Selection of treatment or a decision against treatment should be based on several factors, including the patient's medical condition, the potential for palliation, and the impact of treatment on quality of life.
Surgical Excision of Primary Melanoma
Melanoma skin cancer ---> primary melanoma ---> melanoma treatment ---> melanoma surgery
The primary purpose of a melanoma excision is to prevent local recurrence due to persistent disease. For melanoma in situ, excision margins of 0.5 to 1 cm are indicated. For invasive melanoma, wide excision of the primary tumor, with margins generally ranging from 1 to 2 cm, is indicated for local control. The optimal margin width remains somewhat controversial. The historical approach of excising all primary melanomas with a 3- to 5-cm margin is extinct. At least five randomized controlled trials failed to demonstrate a difference in overall survival or local recurrence with narrow (1 to 2 cm) versus wide (3 to 5 cm) margins. Of note, one trial demonstrated an increased risk of locoregional recurrence with 1 versus 3 cm margins for melanoma more than 2 mm thick.25 Hopefully, results from future randomized prospective trials will demonstrate how narrow a margin is truly safe and efficacious. Until more definitive data become available, current consensus guidelines recommend margins of 1 cm for melanoma of 1 mm or less thick, 1 to 2 cm for 1 to 2 mm thick, and at least 2 cm for greater than 2 mm thick.
Treatment of Regional Metastatic Melanoma
Melanoma skin cancer ---> metastatic melanoma ---> regional metastasis---> melanoma treatment
Surgical excision of metastases to regional lymph nodes is potentially curative therapy. The 5-year survival rate for patients who undergo lymphadenectomy for clinically positive involved nodes (AJCC stage III) ranges from 25% to 70%. In addition, for those patients not cured by lymphadenectomy, resection can avoid potential pain associated with tumor enlargement, skin breakdown, and tumor necrosis. Only 10% of patients who first present with the diagnosis of melanoma have clinical evidence of nodal metastases; approximately 85% have localized disease; the remaining 5% have distant metastases. In less than 3% of patients, a diagnosis of melanoma is made in the absence of a definable primary lesion.28 When patients present with isolated nodal disease from an unknown primary site, the results of lymphadenectomy are similar to those for patients with known primary tumors. For patients with melanoma 1.0 mm thick or greater who present with clinically negative nodes, SLNB should be considered to determine whether therapeutic lymphadenectomy is indicated.
Surgery for Metastatic Melanoma
Melanoma skin cancer ---> metastatic melanoma ---> melanoma treatment ---> melanoma surgery
Surgical excision of recurrent melanoma can be effective for palliation in patients with isolated recurrences in the skin, central nervous system, lung, or gastrointestinal tract. Surgical excision of solitary brain metastases has been shown to provide improved palliation and quality of life compared with brain irradiation. Resection of isolated pulmonary metastases or of subcutaneous recurrences is usually not considered curative but can result in significantly prolonged disease-free survival. Gastrointestinal lesions causing obstruction or bleeding should be considered for resection or bypass to relieve these symptoms.
Chemotherapy for Melanoma
Melanoma skin cancer ---> melanoma treatment ---> melanoma chemotherapy
Melanoma is responsive to few chemotherapeutic drugs. The best single agents for treatment of melanoma are DTIC, the nitrosoureas, vinca alkaloids, and cisplatin, which have objective response rates in the range of 10% to 20%. Conventionally, objective responses have included complete disappearance of all known tumor sites (complete response) and reduction of more than half in all assessable tumor (partial response). Complete responses are rare and nearly always of brief duration (<6months).
Radiation Therapy
Melanoma can respond to radiation therapy. Radiation therapy is commonly used for palliation of bone pain secondary to metastatic disease or brain metastasis. The average survival after brain irradiation for melanoma is approximately 4 months.
Immunotherapy for Melanoma
Melanoma skin cancer ---> melanoma treatment ---> melanoma immunotherapy
The rapid evolution of recombinant DNA technology has resulted in the availability of cytokines, such as the interferons and interleukins, that can be administered to modulate a patient's immune response. These biologic agents have been used in immunotherapeutic trials for metastatic melanoma and demonstrate that an anti-tumor immune response can be generated in selected patients.
The most significant advance in melanoma immunotherapy has been associated with the use of interleukin-2 (IL-2). IL-2 is a cytokine secreted by antigen-activated helper T cells and was initially discovered because it was a T-cell growth factor. Subsequently, it was found to have many other immunologic effects, and it appears to have an important role in the enhancement of immune responses. It has been discovered that the in vivo administration of IL-2 in preclinical animal models resulted in dramatic tumor regression. In clinical studies, the administration of IL-2 resulted in a 15% to 20% response rate in patients with advanced melanoma. Approximately 5% of patients have a complete response which has been durable for prolonged periods. This latter result prompted the FDA to approve IL-2 for the treatment of metastatic melanoma.
IL-2 has been used in combination with other forms of immunotherapy. One example of this is the use of anti-tumor reactive T cells as reagents to treat tumor that is called adoptive immunotherapy. One source of these T cells is from the tumor itself, known as tumor-infiltrating lymphocytes. It has been reported that patients with advanced melanoma treated with the combination of tumor-infiltrating lymphocytes, IL-2, and chemotherapy can result in response rates between 35% and 50%.
Vaccines derived from melanoma tumor cells or extracts of tumor cells have been an emerging field in the treatment of melanoma. The discovery of unique melanoma tumor associated antigens has opened the door for the development of highly specific reagents for tumor vaccines.
Biochemotherapy for Melanoma
Melanoma skin cancer ---> melanoma treatment ---> melanoma biochemotherapy
Combinations of IL-2 and/or IFN- with chemotherapy, known as biochemotherapy, have shown significant improved response rates compared with chemotherapy alone or cytokines alone. As might be expected, these regimens are more toxic than the component therapies by themselves. One of the biochemotherapy regimens that has demonstrated a significant response rate (i.e., 64%, including 21% complete and 43% partial) with moderate toxicity is a combination of cisplatin, vinblastine, dacarbazine, IL-2, and IFN- . A follow-up randomized trial comparing this biochemotherapy regimen to chemotherapy alone indicated that the addition of the cytokines significantly enhanced the anti-tumor activity of the chemotherapy. Biochemotherapy should be considered in patients with advanced melanoma who are thought to be able to tolerate the toxicities of the therapy.
Gene Therapy for Melanoma
Melanoma skin cancer ---> melanoma treatment ---> melanoma gene therapy
The technical feasibility of transfer of genetic material into somatic cells has established a new approach to the treatment of malignancies. Many of the gene therapy strategies for cancer have focused on modulating the host immune response by altering tumor cells to be more immunogenic. A variety of preclinical studies have demonstrated that genetic engineering of tumor cells to secrete or express immunoregulatory peptides (i.e., cytokines, costimulatory molecules, or adhesion molecules) increases the host immune response to these tumors Several clinical studies are evaluating the efficacy of genetic modification of melanoma tumor cells to secrete cytokines that can be administered to patients as tumor vaccines.