Dangers of Tanning

Atypical Mole (Dysplastic Nevus) Syndrome

Familial melanoma and melanoma precursors.
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 United States have familial atypical-mole syndrome with familial melanoma, accounting for approximately 5.5% of all melanomas diagnosed. Hereditary malignant melanoma and atypical moles represent pleiotropic effects of a mendelian autosomal dominant gene with high penetrance.
One study showed that the hereditary cutaneous malignant melanoma/atypical-mole syndrome does not predispose to other cancers.

Definition.
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.

Association with melanoma.
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 United States is approximately 0.8%, or 1 in 125. Persons who have AMs and no family members with the disease have a 6% risk of developing melanoma. Persons who have AMs and a history of melanoma have a 10% risk of getting a second melanoma; persons who have AMs and have a family member with melanoma have a 15% risk. The lifetime risk of melanoma approaches 100% for those people with AMs from families with two or more first-degree relatives who have cutaneous melanoma.
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.

Clinical features of atypical moles

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).

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.

Pictures of Nevi or skin Moles

spitz nevus


halo nevus

lentigo

mongolian spot

Nevus spilus

Nevus spilus

acquired melanocytic nevus

acquired melanocytic nevus

congenital melanocytic nevus

congenital melanocytic nevus

congenital melanocytic nevus

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.

What is Actinic Keratosis

Actinic keratoses are common, sun-induced, premalignant lesions that increase with age. Light-complected individuals are more susceptible than those with dark complexions. Years of sun exposure are required to induce sufficient damage to cause lesions. Actinic keratoses may undergo spontaneous remission if sunlight exposure is reduced, but new lesions may appear. Patients often present with lesions that were first noticed during the summer, suggesting that the lesions may become more active after sunlight exposure.
What are the symptoms and signs of Actinic Keratosis?
Actinic keratoses begin as an area of increased vascularity, with the skin surface becoming slightly rough. Texture is the key to diagnosing early lesions. They are better recognized by palpation than by inspection. Very gradually, an adherent yellow crust forms, the removal of which may cause bleeding . Individual lesions vary in size from 3 to 6 mm. The extent of disease varies from a single lesion to involvement of the entire forehead, balding scalp, or temples. Induration, inflammation, and oozing suggest degeneration into malignancy. Keratin may accumulate and form a cutaneous horn, particularly on the superior aspects of the pinna.
What are the changes of Actinic Keratosis at cellular level?
Histologically, an actinic keratosis consists of atypical squamous cells confined to the epidermis. The follicles are not involved, so there is no follicular plugging. Penetration through the dermoepidermal junction and into the dermis indicates the development of a squamous cell carcinoma.
How is Actinic Keratosis related to squamous cell carcinoma?
After several years, a small percentage of lesions may degenerate into squamous cell carcinomas. A very low yearly transformation rate for single lesions can translate into a substantial lifetime risk of transformation for patients with several actinic keratoses. Up to 60% of squamous cell carcinomas develop from actinic keratosis. Squamous cell carcinomas that evolve from actinic keratosis are not aggressive, but may eventually metastasize. All patients with actinic keratosis should be examined carefully for basal cell carcinomas.
What about Actinic Keratosis treatment?
Because actinic keratoses sometimes undergo spontaneous remission, definitive treatment may be delayed for patients with a few superficial lesions. Small lesions should be reexamined at a later date for spontaneous remission. Patients should make every effort to prevent further sun damage. This does not mean that patients must hibernate for a lifetime, but they should understand techniques to reduce sunlight exposure.
Cryotherapy.
Cryotherapy is the treatment of choice for most isolated, superficial, actinic keratoses. Actinic keratosis resides in the epithelium. Cryotherapy with liquid nitrogen causes the separation of the epidermis and dermis, resulting in a highly specific, nonscarring method of therapy for superficial lesions. Patients with darker complexions may develop hypopigmented areas after freezing, and treating multiple lesions on the faces of such patients may result in white-spotted faces. 5-FU is the best alternative.
Surgical removal.
Individual indurated lesions or those with thick crusts should be removed with minor surgical procedures. It is unnecessary to biopsy lesions less than 0.5 cm. Larger lesions or those occurring about or on the vermilion border of the lips should be examined. Electrodesiccation and curettage easily remove small, thicker lesions. The CO2 laser may be superior to vermilionectomy for actinic cheilitis too extensive to be treated with topical 5-FU.
Tretinoin.
Experience is accumulating that tretinoin (Retin-A) used alone or in combination with topical 5-FU is an effective treatment for certain actinic keratoses. Patients with mild actinic damage who show only erythema and scaling may be treated with tretinoin 0.05% to 0.1% cream applied once a day. If a few focal areas of scale do not respond after 2 to 4 months, they can be treated with cryotherapy. Tretinoin slightly enhances the effectiveness of 5-FU, thereby shortening treatment time, but intensifying tissue reaction and discomfort. Combination therapy is probably not worth the trouble.
Sunscreens.
Regular use of sunscreens prevents the development of solar keratoses. Sunscreens that contain a combination of ingredients to block both the UVA and UVB spectrum of ultraviolet light are most effective. Shade UVA Guard and DuraScreen 30 are examples of commercially available, broad spectrum sunscreens. Sunscreens are best applied in the morning on days when sun exposure is anticipated. Sunscreens should be applied to the face, lower lip, ears, back of the neck, and backs of the hands and forearms. Hats should cover bald heads. The physician should explain that although sunscreens are used, additional lesions may occur, but that many superficial areas of involvement may actually improve.
Acid peels.
Glycolic acid is an alpha hydroxy acid that is useful as a chemical peeling agent. Actinic keratoses involve epidermal hyperplasia and retention of stratum corneum. Alpha hydroxy acids applied topically in high concentrations (30% to 70% glycolic acid) cause epidermolysis and elimination of keratosis. Fluorouracil cream may be used for 5 to 7 days prior to the peel to "light up" and identify the lesions. Glycolic acid is applied with a cotton swab to the keratoses, is left on for 5 to 10 minutes, and is then removed with alcohol. Trichloroacetic acid (35%) and Jessner's solution (14 g of resorcinol, 14 g of lactic acid, and 14 g of salicylic acid dissolved in ethanol to make a final solution of 100 ml) induce a medium-depth peel and equal fluorouracil in efficacy.
Topical chemotherapy with 5-fluorouracil.
5-FU is an effective topical treatment for superficial actinic keratosis. Thicker lesions, especially those on the scalp, may evolve into squamous cell carcinomas and should be treated with more aggressive techniques. The agent is incorporated into rapidly dividing cells, resulting in cell death. Normal cells are less affected and clinically appear to be unaffected. Inflammation is induced during this process. Thick, indurated lesions become most inflamed and may best be managed by surgically removing them before instituting topical chemotherapy. discomfort may be experienced for 1 week or more during periods of intense inflammation. Pain can be minimized if only small areas are treated at one time; however, many patients wish to treat the full face instead of prolonging the unsightly erythema and crusting for weeks. Lesions on the back of the hands and arms require longer periods of treatment than those on the face. Patients with a small number of lesions may be treated during the summer or winter. Patients with a large number of lesions who work outdoors are best treated in the winter. Pharmaceutical companies that manufacture 5-FU supply patient information sheets with color photographs of the various stages of inflammation.
Topical chemotherapy with masoprocol.
Masoprocol (Actinex), a new topical antineoplastic agent, has been approved for treatment of actinic keratoses. A 71.4% reduction in the number of lesions occurs in 1 month when the cream is applied twice a day. Irritation is moderate. Topical 5-FU is more effective.

Nevoid BCC syndrome (Gorlin's syndrome).

This rare disease is inherited as an autosomal dominant trait with high penetrance and variable expressivity. The gene is located on chromosome 9q22.3-q31. It has the following major features: multiple BCCs appear at birth or in early childhood; numerous small pits on the palms and soles (50% to 65%); epithelium-lined jaw cysts, which commonly cause symptoms (65% to 90%); ectopic calcification with lamellar calcification of falx cerebri (80%); and a variety of skeletal abnormalities, especially of the ribs, skull, and spine (70% to 75%). A characteristic facies is present in approximately 70% of patients . Numerous associated anomalies may be present. There is great variation in the number and behavior of the nevoid BCC. Although many patients have no BCCs or just a few, more than 250 BCCs can be present. Locally destructive tumors are not seen before puberty. Aggressive behavior can occur after puberty, and all patients must be followed closely. Most of the highly invasive tumors involve embryonic cleft areas of the face. Development of multiple BCCs is enhanced by exposure to light and x-ray irradiation, but they also occur on unexposed surfaces. Multiple bilateral jaw cysts are the presenting complaint in approximately 50% of patients; the syndrome was discovered by a dentist, R.J. Gorlin. The cysts appear during the first decade of life and displace the child's teeth, often in the premolar area. They cause pain, drainage, and jaw swelling. The occurrence of multiple skeletal anomalies is highly suggestive and may be the earliest clue to the diagnosis of nevoid BCC syndrome in children. Complete or partial bridging of the sella turcica is present in 75% of patients. Splayed and bifurcated ribs occur in 40% of patients.
The initial evaluation of patients suspected of having BCC syndrome should include the following: (1) detailed family history; (2) dental consultations; and (3) x-rays of jaws, skull, chest, spinal column, and hands.

NEVOID BASAL CELL CARCINOMA SYNDROME

SKIN
Multiple nevoid basal cell carcinomas

Pits--palms and soles (50% to 65%)

Milia, cysts (epithelial and sebaceous)


FACE AND MOUTH
Multiple jaw cysts (65% to 90%)

Presenting complaint in 50%

Characteristic facies (70%)

Mandibular prognathism

Broadening of the nasal root (25%)

Frontal/temporoparietal bossing

Ocular hypertelorism


CENTRAL NERVOUS SYSTEM
Lamellar calcification of falx cerebri (80%)

Bridging of the sella turcica (75%)

Mental retardation

Electroencephalographic abnormalities


SKELETAL SYSTEM ANOMALIES (70% TO 75%)
Rib anomalies (55%): bifurcation and splaying (40%), synostotic, or partial agenesis or rudimentary cervical ribs

Vertebrae (65%): kyphoscoliosis (50%), spina bifida occulta (40%)

Shortened metacarpals (usually 4th, 5th, or both) (28%)

Bone cysts--phalanges and other bones (46%)

Many others


OTHERS
Lymphomesenteric cysts

Ovarian fibromas or cysts

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

Skin Cancer spread

Skin cancer is the most common of all cancers. It's highly curable when detected early. Most skin cancers are classified as nonmelanoma, meaning they arise from cells in the skin other than pigment-producing cells called melanocytes. Nonmelanoma cancer isn't likely to spread and it's easily removed.

Melanoma begins in the melanocytes, cells that produce skin color — or melanin. Melanin helps protect deep layers of skin from harmful effects of the sun. A suntan is produced by melanin trying to protect your skin by blocking harmful ultraviolet light, but protection only goes so far. While melanoma accounts for a small percentage of skin cancer, it causes the majority of skin cancer deaths.

Melanoma typically begins as a mole. If you catch it early and it hasn't spread, it can be surgically treated. Here you see the mole being removed, along with surrounding skin. The extra skin is taken to ensure that no cancer cells are left behind.

Melanoma is dangerous because it can spread beyond what you can see, moving deep into your skin where it can gain access to your lymphatic vessels. This allows cancer cells to travel to distant locations in your body. Cancer cells can also travel to different parts of your body by way of your blood vessels.

In this example, melanoma cells migrate to a lymph node. From the lymph node, the melanoma cells can then travel to other parts of your body. Here, you see cancer spreading to the lung.

You don't need to hide indoors to protect your skin from cancer. Wear sunscreen and sun protective clothing and be sure to do skin cancer self-checks. See your health care provider if you find anything suspicious.

Sunscreens

What are Sunscreens?
Sunscreens are products used to protect the skin from the damaging ultraviolet rays of the sun.

What are the ingredients of a sunscreen?
Most sunscreen products contain combinations of ingredients.
They work by absorbing, reflecting, or scattering some or all of the sun's rays.
Many combinations of synthetic and natural ingredients may go into the formulation of a single sunscreen.
Several types of chemicals are used as sunscreens. They vary by the degree of protection they can provide and the types of ultraviolet light they can block:
• Cinnamates, give low levels of protection, and are only effective against UVB light.
• Para-amino benzoic acid (PABA) compounds, are effective only against UVB light.
• Salicylates, octylsalicylate, and homosalate offer moderate levels of protection against both UVA and UVB light, but the range of light waves against which they protect is relatively narrow.
• Benzophenones, protect against a broader range of ultraviolet light than the salicylates and are more useful for broad spectrum protection.
• Physical sunscreens are really sun blockers and include titanium dioxide, red petrolatum, and zinc oxide. Preparations containing these blockers are thick ointments and are usually reserved for skin areas at high risk of burn, such as the nose.
In addition to the chemical used as a sunscreen, the vehicle can be important in determining how well a product works. Unfortunately, thick, greasy ointments seem to work better than vanishing creams, lotions, or liquids.

What is SPF?
Sun Protection Factor
A number telling how well the sunscreen protects against burning. The higher the number, the longer a person can stay in the sun without burning.

Sunlight effects upon the skin

Ultraviolet radiation (UVR) comprises only about 5% of sunlight, with visible light and infrared radiation making up the remaining 95%. However, it is UVR which is chiefly responsible for the harmful effects of sunlight exposure. On a sunny day, UVA (315-400 nm) accounts for at least 95% of UVR, and UVB (280-315 nm) no more than 5%. UVR has acute and chronic effects on the skin.
Acute effects
Erythema (sunburn)
Sunburn or erythema can vary in intensity from mild redness to oedema, blistering and peeling. Susceptibility to sunburn and tanning depends on the skin phototype of the individual. UVB is much more effective at inducing erythema than UVA. UVB accounts for only about 5% of solar radiation but it contributes to about 80% of the erythema caused by sunlight. Experiments suggest that the synthesis and release of prostaglandin E2 (PGE2), following cyclooxygenase-2 (cox-2) gene activation, and nitric oxide within the dermis are responsible for UV-induced erythema.
Melanogenesis (tanning)
Skin colour is genetically controlled but can be enhanced by UVR exposure. Each skin phototype has a different ability to tan. Tanning and epidermal hyperplasia following UVR exposure protects against erythema and burning, but maintaining this requires repeated exposures, which can result in the chronic effects of photodamage.
Skin phototypes
Skin phototype Response to UVR exposure
I White skin, always burns, never tans (Celtic)
II White skin, burns initially, tans with difficulty
III White skin, rarely burns, tans easily
IV White skin, never burns always tans (Mediterranean)
V Brown skin (Asian)
VI Black skin
Immunosuppression
Both UVA and UVB exposure suppress cutaneous cell-mediated immunity in humans. This effect is significantly higher in skin types I/II than in types III/IV. UVR-induced immunosuppression is thought to play an important role in the emergence of skin cancer, which explains the increased risk of skin cancer in individuals with skin types I/II who have a history of repetitive and intense UVR exposure.
Chronic effects
Photoageing
Photoageing results in dry, deeply wrinkled, inelastic, leathery skin with telangiectasia, mottled pigmentation, freckling and lentigines. Repeated long-term UVR exposure, especially UVB, results in changes within the dermal connective tissue. There is elastosis and degradation and disorganization of collagen fibrils. It is thought that UVR-induced metalloproteinases (endopeptidases that degrade structural proteins) degrade the dermal matrix, which then undergoes imperfect repair.
Photocarcinogenesis
Skin cancer is the long-term result of a complex interaction between UVR exposure and genetics. Genetic factors include skin phototype, DNA repair capacity and immunocompetence. DNA damage occurs following UVR, and this is repaired by nucleotide excision repair. Repeated UV exposure together with suboptimal repair results in the clonal expansion of cells with mutated oncogenes leading to melanoma and non-melanoma skin cancer. Studies have shown that squamous cell carcinomas develop as the consequence of accumulated sun exposure, whereas melanoma and basal cell carcinomas are more dependent on specific patterns of childhood and intermittent high-dose sun exposure. Other important risk factors for the development of skin cancer include UVR-induced immunosuppression as well as immunosuppressant drugs as seen in organ transplant patients.
Photodermatoses
Photodermatoses (diseases caused by sunlight) can be divided into two main categories, those in which the sunlight has a primary role in the condition (primary photosensitivity) and those in which the sunlight acts as an exacerbating factor (secondary photosensitivity).

Tanning and skin cancer facts

There is a popular belief that suntanned skin is healthy and attractive. Many people spend more time in the sun than is good for their skin trying to achieve a fashionable tan.
A considerable percentage of the white skinned population admits to tanning at least once a year either in the sun or in tanning beds.
In a magazine survey, two thirds of teens said they "look better with a tan and feel healthier, more sophisticated," and half said they looked "more athletic".
Tanned skin is thought to be associated with swimming pools, backyard barbecues, dinner parties, and exotic vacations. In this context, tanned skin took on a feature of attractiveness as a signal of being well-traveled, cultured, and supposed evidence of leisure wealth. It also became a signal of health and strength as the bodybuilding and fitness industries increasingly promoted tanning to highlight muscle tone and definition.
Suntan is caused by an increased release of the pigment melanin into the skin's cells after exposure to ultraviolet radiation.
There is convincing evidence from many studies that frequent exposure to any form of UV radiation (solar or artificial) increases the risk for the development of skin cancer.
Preventive measures include avoiding sun exposure between 10 a.m. and 4 p.m, wearing a hat and anti-UV sunglasses which can provide almost 100% protection against ultraviolet radiation entering the eyes and applying a sunscreen that blocks both UVA and UVB rays.

Melanocyes and Melanin

Most people's skin darkens when exposed to UV light, giving them more protection when it is needed. This is the physiological purpose of sun tanning.
Freckles and moles are formed where there is a localized concentration of melanin in the skin.
So what is Melanin?
Melanin has a photoprotective role.
It is produced by melanocytes, through a process called melanogenesis. Melanocytes are cells located in the bottom layer of the skin's epidermis. Although human beings generally possess a similar concentration of melanocytes in their skin, the melanocytes in some individuals and ethnic groups more frequently or less frequently express the melanin-producing genes, thereby conferring a greater or lesser concentration of skin melanin.
Once made, melanin is moved along arm-like structures called dendrites in a special container called a melanosome which is shipped to the keratinocytes. Melanosomes are vesicles or packages of the chemical inside a plasma membrane. The melanin is in organelles called "melanosomes", that are organized as a cap protecting the nucleus of the keratinocyte.
Because melanin is an aggregate of smaller component molecules, there are a number of different types of melanin with differing proportions and bonding patterns of these component molecules. Both pheomelanin and eumelanin are found in human skin and hair, but eumelanin is the most abundant melanin in humans.
Eumelanin is found in hair and skin, and colors hair grey, black, yellow, and brown. In humans, it is more abundant in peoples with dark skin. There are two different types of eumelanin. The two types are black eumelanin and brown eumelanin. Black eumelanin is the darkest, brown eumelanin is lighter than black eumelanin. black eumelanin is in mostly non-Europeans and aged Europeans, while brown eumelanin is in mostly young Europeans. A small amount of black eumelanin in the absence of other pigments causes grey hair. A small amount of brown eumelanin in the absence of other pigments causes yellow (blond) color hair.
Pheomelanin is also found in hair and skin and is both in lighter skinned humans and darker skinned humans. But in general women have more pheomelanin than men, and thus women's skin is generally redder than men's. Pheomelanin imparts a pink to red hue and, thus, is found in particularly large quantities in red hair. Pheomelanin is particularly concentrated in the lips, nipples, glans, and vagina. Pheomelanin also may become carcinogenic when exposed to the ultraviolet rays of the sun.
Melanocytes insert granules of melanin into specialized cellular vesicles called melanosomes. These are then transferred into the other skin cells of the human epidermis. The melanosomes in each recipient cell accumulate atop the cell nucleus, where they protect the nuclear DNA from mutations caused by the ionizing radiation of the sun's ultraviolet rays. When ultraviolet rays penetrate the skin and damage DNA; fragments from damaged DNA will trigger melanogenesis and cause the melanocyte to produce melanosomes, which are then transferred by dendrite to the top layer of keratinocytes.
People whose ancestors lived for long periods in the regions of the globe near the equator generally have larger quantities of eumelanin in their skins. This makes their skins brown or black and protects them against high levels of exposure to the sun, which more frequently results in melanomas in lighter skinned people.

What is Skin phototype

Skin phototype depends on the amount of melanin pigment in the skin. It is assessed on a scale from 1 to 6. Melanin is produced by melanocytes, through a process called melanogenesis.
There are both basal and activated levels of melanogenesis; lighter-skinned people generally have low basal levels of melanogenesis, and exposure to UV radiation generally causes increased melanogenesis.
There are typically between 1000 and 2000 melanocytes per square millimeter of skin. Melanocytes comprise from 5% to 10% of the cells in the basal layer of epidermis. Although their size can vary, melanocytes are typically 7 micrometers in length.
The difference in skin color between fair people and dark people is due not to the number (quantity) of melanocytes in their skin, but to the melanocytes' level of activity..

Skin Phototype	Typical Features	Tanning ability
I	Pale white skin, blue/hazel eyes, blond/red hair	Always burns, does not tan
II	Fair skin, blue eyes	Burns easily, tans poorly
III	Darker white skin	Tans after initial burn
IV	Light brown skin	Burns minimally, tans easily
V	Brown skin	Rarely burns, tans darkly easily
VI	Dark brown or black skin	Never burns, always tans darkly