Skin Moles

Congenital skin moles are defined as benign nevomelanocytic proliferations that are present at birth. Occasionally, skin moles that are clinically and histologically indistinguishable from congenital skin moles that develop in children during the first 2 years of life. This type is referred to as congenital nevus tardive and can be treated similar to a congenital skin mole.
Congenital skin moles are present in approximately 1% of newborn infants and are important for three reasons. First, they can be cosmetically disfiguring, depending on the size and location. Second, congenital skin moles, particularly large ones, are at an increased risk of developing melanoma. Third, and most importantly, melanoma that develops in large congenital skin moles most often occurs deep within the dermis where it is not easily detectable on clinical examination until at an advanced stage.
The cause of congenital skin moles is uncertain. The melanocytes of the skin originate in the neuroectoderm, although the specific cell type from which they are derived is unknown. One theory of the origin of melanocytes in the skin considers that the pluripotential nerve sheath precursor cells migrate from the neural crest to the skin along paraspinal ganglia and peripheral nerve sheaths, and differentiate into melanocytes upon reaching the skin.
One explanation for the development of a congenital skin mole is that some type of external insult results in a mutation that disrupts the normal morphogenesis of the embryonic neuroectoderm and migration of precursor cells to the skin.
Based on the observation of divided congenital skin moles found on adjacent parts of the upper and lower eyelids, it has been concluded that they develop between the 9th and 20th week of fetal development, as this is the period during which the eyelids are fused.
Congenital skin moles have been classified into three groups. The most common method of classification is based on the size of the lesion during infancy. Small congenital skin moles are defined as those lesions less than 1.5 cm at the greatest diameter, medium congenital skin moles as those between 1.5 and 20 cm, and large or giant congenital skin moles as those with a diameter of 20 cm or greater. Large congenital skin moles may have smaller surrounding satellite skin moles . Congenital skin moles have also been classified based on the ease of surgical removal. Small congenital skin moles can usually be removed with simple excision. Medium congenital skin moles, depending on size, may require skin grafts or flaps for closure. In cases where large congenital skin moles can be removed, they often require staged excisions using tissue expanders and skin grafts. Other classifications take into account the percentage of body surface area covered by a lesion based on anatomic location.
Distinguishing congenital from acquired skin moles on the basis of histology is not always possible. However, a set of distinctive histological features may help differentiate between the two. Congenital skin moles classically display the following elements: (1) the presence of nevus cells within the deeper two-thirds of the dermis with possible extension into the subcutaneous tissue, (2) involvement of nevus cells around and within neurovascular structures and deep dermal appendages including hair follicles, arrector pili muscles, sebaceous glands, nerves, and walls of blood vessels, (3) infiltration or splaying of nevus cells between collagen bundles of the reticular dermis either as single cells or cords of cells, and (4) a perifollicular and perivascular distribution of nevus cells simulating an inflammatory reaction. Although these features are not pathognomonic for congenital skin moles , they are most consistently observed in large congenital skin moles. Small and medium congenital skin moles may show all, some, or none of these features and may be histologically indistinguishable from acquired skin moles. In contrast to congenital skin moles, acquired skin moles are usually composed of nevomelanocytes that do not involve the appendages and are limited to the papillary and upper reticular dermis. Large congential skin moles may demonstrate a number of patterns including intradermal or compound mole. The nevus cells of congenital skin moles are also typically positive for the markers S-100, Melan-A, and HMB-45. In the absence of a clear history, the aforementioned features can be useful in establishing the likelihood that a skin mole is a congenital rather than an acquired one.
Treatment of congenital skin moles is guided by two factors: risk of cancerous change and cosmetic impact. Many treatment options have been used in an attempt to reduce the rate of melanoma and/or improve the cosmetic appearance of patients with congenital skin moles. Different treatment strategies have included careful monitoring, serial photography, surgical excision, dermabrasion, curettage, and laser treatment.
Many factors must be taken into consideration when managing these lesions, including the perceived risk of melanoma, size and location of the lesion, cosmetic impact, proximity to vital structures, psychosocial effects, risks of invasive intervention, and likely cosmetic outcome. An open discussion with patients and/or family members, including treatment options, realistic outcome expectations, and the relative scarcity of evidence-based data is essential.
Although the great majority of patients with congenital skin moles of any size will never develop melanoma, the presence of large congenital skin moles clearly places an individual at increased risk of cancerous change.
Because melanoma develops at an early age in large congenital skin moles and often originates deep to the epidermis where it cannot easily be detected on clinical examination, watchful waiting is not the recommended approach. Surgical excision of these lesions at an early age remains the mainstay of treatment for those seeking prophylactic therapy. One study, which examined the physical and psychosocial effects of large congenital skin moles and their surgical removal, suggests 6 to 9 months as an optimal age for surgical excision. Unfortunately, surgical excision down to fascia does not entirely eliminate the risk of melanoma as it is not possible to ensure the removal of all nevus cells, some of which may be found deep to the fascia within muscle and nerve. Additionally, excisions of very large congenital skin moles that pose the greatest risk of melanoma, are often very difficult or impossible, and frequently produce unacceptable cosmesis. There is also a lack of published evidence to quantify the reduction of melanoma risk following prophylactic surgery.
Patients with small congenital skin moles appear to be at an increased lifetime risk of melanoma, although not to the same extent as patients with large congenital skin moles. Given the current evidence, watchful waiting with regular
follow-up, dermatoscopic and photographic evaluation, and monitoring by parents is an appropriate treatment strategy for most of these lesions. Unlike the case of large congenital skin moles, careful clinical observation will detect cancerous changes in these lesions because melanomas arising in small congenital skin moles are almost always epidermal in origin.
When prophylactic removal is desired, it can generally be delayed until just prior to puberty because melanoma in these lesions develops almost exclusively during adulthood.
Treatment of medium congenital skin moles is the most difficult of the three classes of congenital skin moles. While they do not appear to present the same melanoma risk as large congenital skin moles, an accurate risk assessment has not been established. There is also insufficient data to suggest that one treatment strategy is superior.
Some have suggested taking a biopsy of these lesions prior to excision. If histologic patterns are similar to those of acquired skin moles, then the lesions could be managed similarly to the case of small congenital skin moles. If patterns of deep dermal growth are observed, as in large congenital skin moles, the risk of clinically undetectable melanoma presumably would be higher and warrant prophylactic excision as early as possible.
Because the risk of prepubertal melanoma in these lesions is small, others have suggested excision of these lesions in the pubertal years when the risks of anesthesia are lower than during childhood.

The blue skin mole is a benign neoplasm, also called blue nevus or Jadassohn-Tièche nevus, appears clinically as a dark-blue or blue-black smooth nevus formed by melanin-heavily pigmented spindle cells in the middle and lower two-thirds of the dermis. Clinically, the blue nevus appears as a slate blue or bluish black, sharply circumscribed, flat or slightly elevated nodule, occurring on any area of the body. It originates from mesodermal cells. The common blue nevus is always benign. Cellular blue nevus is larger, especially on buttocks and can degenerate into malignant melanoma.
Blue skin moles are present in fewer than 1 in 3000 newborns, in about 1 in 1000 during the first 5 years of life, and in 1 to 2 percent of white school children, and 0.5 to 4 percent of healthy white adults. They are said to be uncommon in darkly pigmented persons. The vast majority of blue skin moles are single, small, deep-blue macules or papules about 1 to 2 mm in diameter.
Common blue skin moles are usually acquired, singular, asymptomatic blue, blue-gray, or blue-black papules, usually less than 10 mm in diameter. The blue-gray color of blue skin moles is an optical effect of dermal melanin viewed through the overlying skin. The longer wavelengths of visible light penetrate the deep dermis and are absorbed by black dermal melanin, but the shorter (blue) wavelengths do not penetrate deeply enough to be absorbed by melanin and are thus reflected back to the observer's eye, giving a blue-gray cast to the deeply situated melanin. Common blue skin moles occur anywhere, but about half the reported cases present on the dorsa of hands and feet. The common blue nevus occasionally may have a target-like appearance, with a blue-gray central nodule, a flesh-colored or hypopigmented surrounding area, and a blue-black rim. The target blue nevus occurs mostly on the hands and feet but also on the back and perianal area. Common blue skin moles occasionally may have satellite lesions that may be mistaken for melanoma metastasis.
Cellular blue skin moles are blue-gray or blue-brown nodules or plaques 1 to 3 cm in diameter, occasionally larger. Their surface is usually smooth but may be irregular. About half the cases are located on the buttocks or sacrum. Malignant blue nevus may develop in contiguity with a cellular blue nevus or de novo. Malignant blue nevus presents as an expanding dermal nodule with or without ulceration.
A common blue nevus that is stable for many years in an adult usually requires no therapy. Sudden appearance of a blue nodule, expansion of a preexisting blue nodule, a congenital blue nodule, or a relatively large blue nodule or plaque greater than 10 mm in diameter demands histopathologic examination. Excision should include subcutaneous fat to ensure complete removal of deep dermal melanocytes, which are frequently present in the subcutaneous tissue of cellular blue nevus. Cellular blue nevus should be evaluated for excision because of its malignant potential.

What is punch biopsy?
Punch biopsy is one of the most widely used dermatologic procedures in primary care medicine. This technique obtains a full-thickness skin specimen for histologic assessment. A properly performed punch biopsy frequently yields useful diagnostic information. The technique is simple, rapid, and generally results in an acceptable final cosmetic appearance at the site.

What are the indications of punch biopsy?
Evaluation of skin tumors, diagnosis of skin disorders, removal of small skin lesions such as intradermal nevi and diagnosis of atypical appearing lesions.

How is punch biopsy performed?
Punch biopsy is performed with a circular blade known as a trephine, which is attached to a pencil-like handle. The instrument is rotated using downward pressure until the blade penetrates into the subcutaneous fat. A cylindrical core of tissue is then cut free and placed in formalin for transfer to the laboratory. Most 3- or 4-mm punch biopsy sites are closed with a single suture. The 2-mm punch biopsy sites frequently do not require suture closure, and Monsel's solution can be used for hemostasis if the wound is allowed to granulate.

Why is punch biopsy performed?
Punch biopsy is generally performed to evaluate lesions of uncertain origin or to confirm or exclude the presence of malignancy. This biopsy technique is considered the method of choice for many flat lesions. Suspected melanomas can be evaluated by this technique, especially when the lesion is too large for easy removal. The yield may be improved if the most suspicious or abnormal-appearing area (darkest, most raised, or most irregular contour) is biopsied. If the suspicion for melanoma is high, it is preferable to perform excisional biopsy to have the entire lesion available for evaluation.

What are the disadvantages of performing punch biopsy for suspected cancer lesions?
Punch biopsy used for basal and squamous cell carcinoma has one disadvantage. After these cancers have been biopsied using punch technique, the physician is obligated to perform a definitive excisional technique. Superficial techniques that are frequently employed for these lesions, such as curettage and electrodesiccation, may miss cells that have been driven deeper by the punch instrument. Physicians should not fear performing punch biopsy on a melanoma, because the biopsy does not alter the natural course of the disease, and a prompt biopsy expedites definitive treatment.

What should physicians be oriented of when performing a punch biopsy?
Physicians should be aware of the underlying anatomy when performing a punch biopsy. Certain areas of the body where there is little subcutaneous tissue pose the greatest threat of damaging underlying structures such as arteries, tendons, or nerves. Punch biopsy on the upper cheek can damage the facial or trigeminal nerves, and punch biopsy of the lateral digits or of the thin eyelids should be approached with great caution.

What are the implications of these factors on performing a punch biopsy?
Lesions overlying anatomic structures likely to be damaged by full-thickness skin biopsy: on the eyelid (globe), on the dorsum of the hand in elderly patients (tendons), or on the upper cheek (facial nerve) or fingers (digital nerves and arteries) should be contrindicated. Also foot and toe lesions in elderly patients or those with peripheral vascular disease.

Atypical moles are also called Dysplastic nevi. The atypical mole is a skin mole with irregular border, larger size, and has a collection of distinctive histological features.
Prevalence: 2–8% of whites have atypical moles. They begin developing during puberty and continue to appear throughout life. Atypical moles may be sporadic or have autosomal dominant inheritance (atypical mole syndrome).
Development: Hormones and sun exposure appear to be the major causative factors.
On examination: atypical moles and early malignant melanomas can be identified by the ABCDE rule; the criteria are most pronounced in malignant melanoma.
– Asymmetry.
– Border: irregular.
– Color: multiple colors.
– Diameter: more than 6mm.
– Elevating or Enlarging: a papule mole is usually harmless; a flat mole that grows or develops a nodular component is suspicious.
Atypical moles may have a “fried egg” appearance: broad flat moles (white of egg) with raised central portion (egg yolk). Sporadic atypical moles are commonly found on the palms, soles, breast, umbilicus, genital, and perianal regions.
Histopathology: The histological features of atypical moles are highly controversial. They include: Junctional proliferation of melanocytes extending beyond the dermal component of the mole (shoulder effect) often with fusion of adjacent aggregates (bridging). Melanocytes in aggregates are often spindle-shaped. Fibrosis around the aggregates (lamellar fibrosis). Lymphocytic infiltrates. Atypia of melanocytes: most controversial point; some groups say no atypia; others grade the degree of atypia (mild, moderate, severe).
NB: Many studies have shown that these criteria, greatly simplified here, are not reproducible, even between expert observers, or even by the same observer over a period of time. Almost every flat mole shows some of these features under the microscope.
Similar conditions: Common mole, malignant melanoma.
Treatment: If a patient has only one or a small number of atypical moles, excision is the simplest approach.

Skin moles
The term ‘mole’ refers to a lesion, often present at birth, which has a local excess of one or more normal constituents of the skin. Skin moles (nevi) are localized benign proliferations of melanocytes. Their classiflcation is based on the site of the aggregations of nevus cells.

Causes of skin moles.
The cause is unknown. A genetic factor is likely in many families, working together with excessive sun exposure during childhood.

Classiflcation of skin moles.
Congenital melanocytic skin moles
Acquired melanocytic skin moles
Junctional mole
Compound mole
Intradermal mole
Spitz mole
Blue mole
Atypical melanocytic mole

With the exception of congenital skin moles, most appear in early childhood, often with a sharp increase in numbers during adolescence. Further crops may appear during pregnancy, oestrogen therapy or, rarely, after cytotoxic chemotherapy and immunosuppression, but new lesions come up less often after the age of 20 years. Skin moles in childhood are usually of the junctional’ type, with proliferating melanocytes in clumps at the dermo-epidermal junction. Later, the melanocytes round off and ‘drop’ into the dermis. A ‘compound’ mole has both dermal and junctional components. With maturation the junctional component disappears so that the melanocytes in an intradermal’ mole are all in the dermis.

Presentations of skin moles.
Congenital skin moles.
These are present at birth or appear in the neonatal period and are seldom less than 1 cm in diameter. Their color varies from brown to black or blue-black. With maturity some become protuberant and hairy, with a cerebriform surface. Such lesions
can be disflguring, e.g. a ‘bathing trunk’ mole, and carry an increased risk of malignant transformation.
Junctional skin moles.
These are roughly circular macules. Their color ranges from mid to dark brown and may vary even within a single lesion. Most skin moles of the palms, soles and genitals are of this type.
Compound skin moles.
These are domed pigmented nodules of up to 1 cm in diameter. They may be light or dark brown but their colour is more even than that of junctional skin moles. Most are smooth, but larger ones may be cerebriform, or even hyperkeratotic and papillomatous; many bear hairs.
Intradermal skin moles.
These look like compound skin moles but are less pigmented and often skin-coloured.
Spitz moles (juvenile melanomas).
These are usually found in children. They develop over a month or two as solitary pink or red nodules of up to 1 cm in diameter and are most common on the face and legs. Although benign, they are often excised because of their rapid growth.
Blue moles.
So-called because of their striking slate grey-blue colour, blue skin moles usually appear in childhood and adolescence, on the limbs, buttocks and lower back. They are usually solitary.
Mongolian spots.
Pigment in dermal melanocytes is responsible for these bruise-like greyish areas seen on the lumbosacral area of most Down’s syndrome and many Asian and black babies. They usually fade during childhood.
Atypical mole syndrome (dysplastic nevus syndrome).
Clinically atypical skin moles can occur sporadically or run in families as an autosomal dominant trait, with incomplete penetrance, affecting several generations. Some families with atypical skin moles are melanoma-prone. Genes for susceptibility to melanoma have been mapped to chromosomes 1p36 and 9p13 in a few of these families. The many large irregularly pigmented skin moles are most obvious on the trunk but some may be present on the scalp. Their edges are irregular and they vary greatly in size, many being over 1 cm in diameter. Some are pinkish and an inflamed halo may surround them. Some have a mamillated surface. Patients with multiple atypical melanocytic or dysplastic skin moles with a positive family history of malignant melanoma should be followed up 6-monthly for life.

Differential diagnosis of skin moles.
* Malignant melanomas. This is the most important part of the differential diagnosis. Melanomas are very rare before puberty, single and more variably pigmented and irregularly shaped.
* Seborrhoeic keratoses. These can cause confusion in adults but have a stuck-on appearance and are warty. Tell-tale keratin plugs and horny cysts may be seen with the help of a lens.
* Lentigines. These may be found on any part of the skin and mucous membranes. More profuse than junctional skin moles, they are usually grey-brown rather than black, and develop more often after adolescence.
* Ephelides (freckles). These are tan macules less than 5 mm in diameter. They are confined to sun-exposed areas, being most common in blond or red-haired people.
* Hemangiomas. Benign proliferations of blood vessels, including hemangiomas and pyogenic granulomas, may be confused with a vascular Spitz mole or an amelanotic melanoma.

Histology of skin moles.
Most acquired lesions are orderly nests of benign nevus cells that are seen in the junctional region, in the dermis, or in both. However, some types of skin moles have their own distinguishing features.
In congenital skin moles the nevus cells may extend to the subcutaneous fat, and hyperplasia of other skin components (e.g. hair follicles) may be seen.
A Spitz mole has a histology worryingly similar to that of a melanoma. It shows dermal oedema and dilatated capillaries, and is composed of large epithelioid and spindle-shaped nevus cells, some of which may be in mitosis.
In a blue mole, nevus cells are seen in the mid and deep dermis.
The main features of clinically atypical (‘dysplastic’) skin moles are lengthening and bridging of rete ridges, and the presence of junctional nests showing melanocytic dysplasia (nuclear pleomorphism and hyperchromatism). Fibrosis of the papillary dermis and a lymphocytic inflammatory response are also seen.

Complications of skin moles.
* Inflammation. Pain and swelling are common but are not features of cancerous transformation. They are caused by trauma, bacterial folliculitis or a foreign body reaction to hair after shaving or plucking.
* Depigmented halo. So-called ‘halo moles’ are uncommon but benign. There may be vitiligo elsewhere. The mole in the centre often involutes spontaneously before the halo repigments.
* Malignant change. This is extremely rare except in congenital skin moles, where the risk has been estimated at between 3 and 6% depending on their size, and in the atypical skin moles of melanoma-prone families. It should be considered if the following changes occur in a skin mole:
* itch;
* enlargement;
* increased or decreased pigmentation;
* altered shape;
* altered contour;
* inflammation;
* ulceration; or
* bleeding.
If changing lesions are examined carefully, remembering the ‘ABCDE’ features of malignant melanoma, few malignant melanomas should be missed.

Treatment of skin moles.
Excision is needed when:
1- a mole is unsightly;
2- malignancy is suspected or is a known risk, e.g. in a large congenital mole; or
3- a mole is repeatedly inflamed or traumatized.

The ABCDE of cancerous transformation in a skin mole
Asymmetry
Border irregularity
Colour variability
Diameter greater than 0.5 cm
Elevation irregularity

The atypical mole is a special kind of dysplastic melanocytic nevus, with clinical and microscopic features suggestive of an intermediate form between the common acquired mole and melanoma. Atypical skin moles are important markers for both familial and non familial melanoma. As many as 50% of patients with “sporadic” melanoma have been observed to have atypical skin moles. The incidence of atypical skin moles in the general population has been estimated to be 1.8% to 10% and possibly as high as 19%. The presence of atypical skin moles has been established as an independent risk factor for melanoma, along with several other cutaneous traits, including red or blonde hair, solar lentigines, skin type 1 or 2, and increased numbers of common acquired melanocytic nevi. One study found the adjusted relative risk of melanoma to be 2 for a single atypical mole and 12 for 10 or more atypical skin moles. Another found a relative risk of 1.6 when one to four atypical skin moles were counted and 6.1 for five or more atypical skin moles. The risk ofmelanoma attributable to atypical skin moles may be further exacerbated by the coexistence of other melanoma risk factors, such as skin type 1 or 2. The increased risk for melanoma is particularly true in the setting of the atypical mole syndrome (AMS). AMS encompasses individuals with multiple atypical skin moles arising sporadically or in a setting of a family history of atypical skin moles or melanoma. AMS has been divided into a number of forms. Type A is sporadic atypical mole without melanoma; type B is familial atypical mole without melanoma; type C is sporadic atypical mole with a personal history of melanoma; type D-l is familial atypical mole with one family member with melanoma; and type D-2 is familial atypical mole with two or more family members with melanoma. Meticulous screening of family members may demonstrate that presumptive cases of sporadic AMS are actually familial. All patients with AMS have an increased risk for developing melanoma, although the magnitude of the risk varies among the AMS types. The relative risk of melanoma is least in patients with AMS types A and B, and has been estimated to be 7 with a cumulative lifetime risk of 6%. The relative risk of melanoma in type D-2 patients may be as high as 1000 or greater compared with the general population. Individuals with AMS also appear to be at an increased risk for multiple primary cutaneous melanomas.One study found a 35.5% cumulative 10-year risk of developing a second melanoma in those with AMS and a history of melanoma as compared with a 17% 10-year risk of developing a second melanoma in those with a history of melanoma but without AMS. Patients with AMS may also be at increased risk of conjunctival and intraocular melanoma. The recognition of AMS may allow early detection of melanoma and identification of those at risk and provide the opportunity for the initiation of preventive measures. A great deal of discussion has centered on the validity of the atypical mole as a distinct entity and its potential for progression to melanoma. Much disagreement over its nature stems from a lack of uniform clinical and microscopic criteria to define it. Atypical skin moles generally demonstrate both clinical and microscopic evidence of distorted and disordered architecture.  

Moles cancer has been associated with large congenital skin moles, acquired atypical skin moles, or arise de novo.
Cancerous change in a mole may be in the form of:
1. Asymmetry. Irregular pigmentation with darkening of one portion of the mole, a small dark elevated papule within an otherwise flat papule, or flaking, scaling, ulceration or bleeding
2. Border irregularity. tumor appears to be growing in one direction with scalloped edges
3. Color variation. Appearance of black, dark brown or admixture of red, white and black
4. Diameter more than 6mm; most benign acquired skin moles are less than 6mm
5. Symptoms: burning, itching, or tenderness

* Risk factors:
1. New or changing mole
2. Age more than 15 years
3. Atypical skin moles, prior melanoma and familial melanoma
4. Large congenital mole
5. 50 skin moles, more than 2mm in diameter
6. 12 skin moles, more than 6mm in diameter
7. Light skin color
8. Marked freckling
9. Sun sensitivity
10. Excessive sun exposure

* Associations:
1. Family history of melanoma
2. Presence of multiple atypical skin moles (atypical mole syndrome)
3. Xeroderma pigmentosum
4. Transplacental spread of maternal melanoma

Pathogenesis:
* Genetic factors with resultant progressive changes in DNA and inability to repair DNA
* Familial cutaneous malignant melanoma (OMIM no. 15560) can be caused by germline mutations
in CDKN2A on chromosome 9p21 and CDK4 on 12q14 and 1p36

Diagnosis of moles cancer:
* Clinical features
* Histology: increased numbers of atypical basal melanocytes with atypical nuclei of different sizes, epidermotropism, nest of melanocytes with variation in size and shape, asymmetrical no maturation of melanocytes, signs of regression

Differential diagnosis:
* Spitz mole
* Acquired atypical mole
* Blue mole
* Traumatic hemorrhage (especially under the nails, on the heels, or on the mucous membranes)
* Septic granuloma

Treatment of moles cancer:
* Excision with wide margins based on microscopic depth of melanoma cells:
1. In situ: 2–5mm excision margin
2. Less than 1 mm: 1 cm excision margin
3. 1–2mm: 1–2 cm excision margin
4. 2.1–4mm: 2–3 cm excision margin
5. More than 4mm: 2–3 cm excision margin
* Adjunctive treatments: interferon, chemotherapy

Moles cancer survival:
* Influenced by depth of the tumor and involvement of lymph nodes
* Five year survival (in general; many factors influence staging): stages I–II: 79%; stage III: 13–69%; stage IV: 6%

The vast majority of acquired skin moles require no treatment. Indications for removal of benign-appearing moles may include cosmetic concerns or continual irritation that could be mistaken for a changing mole. Moles with cancerous features need to be excised. A photographic medical record can play a critical role in identifying changes that might not have been detected otherwise. Complete removal of skin moles is best accomplished by elliptical excision. Leaving a partially excised mole, regardless of the initial pathology, is fraught with potentially alarming consequences of repigmentation and/or regrowth (pseudomelanoma). Incisional biopsy, even for melanoma, is necessary at times, particularly for moles that cannot be excised easily and that require histopathologic diagnosis.
Destructive modes of removal (electrodesiccation, cryotherapy, dermabrasion, and laser) should be considered very carefully if used in the treatment of skin moles. They have the definite disadvantage of not providing tissue for histopathology.
Although dermabrasion has been used to eliminate pigmentation of skin moles, residual nevus cells in the dermis are to be expected, cosmetic outcome is often unpredictable, and recurrence with susceptible features may complicate future management.
Laser treatment of skin moles has the theoretical risk of cancerous change, but there is no proof for this.

Common features:
Typical acquired skin moles vary considerably in their gross features. In general, appearance to the naked eye is orderly; i.e., lesions have a homogeneous surface and coloration pattern, round or oval shape, regular outlines, and relatively sharp border. Typical acquired skin moles may be papillomatous, dome-shaped, pedunculated, or flat-topped and usually are flesh-colored, pink, or brown.
Clinico-pathological correlation:
More elevated acquired skin moles tend to be more lightly pigmented, and flatter acquired skin moles tend to be more darkly pigmented. More elevated and less pigmented lesions tend to have a prominent intradermal nevus component, whereas flatter and darker lesions have a more prominent junctional component and a less prominent dermal component. Skin moles on palms and soles, even compound skin moles, may not distort the skin surface, perhaps because of a thickened stratum corneum in these sites.
Special features:
Dark pigmentation:
Very dark brown and black are unusual colors for typical acquired skin moles in lightly pigmented people. In contrast, dark pigmentation is usual for Typical acquired skin moles in people who have darkly pigmented skin. Very dark brown and black in skin moles on acral and mucosal surfaces and nail apparatus should be viewed with suspicion regardless of normal skin color.
Other colors:
Blue, gray, red, and white areas in a mole are not typical features and ought also to be viewed with suspicion.
Hair quality:
The surfaces of skin moles may reveal hair that is less than, equal to, or greater than that of surrounding skin. Hair in skin moles may be coarser, longer, and darker than that in surrounding skin.
Site specific:
Lesions on palms and soles are usually hairless. Size, shape, skin markings, and hair quality of skin moles in darkly pigmented races are similar to those in whites.
Extent of lesion:
Skin moles of the nail apparatus may be a dark or light brown, extending from the nail matrix to the distal edge of the nail plate; extension of the pigmentation onto the skin of the nail fold or beyond the distal nail groove should be considered suspicious for melanocytic dysplasia or malignant melanoma.

Any skin mole, by definition, is benign. A skin mole, is a benign proliferation of melanocytes in the epidermis, epidermis and dermis, or dermis alone. In general, a skin mole is a small (less than 6 mm), symmetric, well-circumscribed proliferation of nested melanocytes, and the melanocytes that are deepest in the dermis are smaller than superficial melanocytes, a process known as maturation.

Typical Acquired Mole is a proliferation of nevomelanocytes in the epidermis (junctional), dermis (intradermal), or both areas (compound). The nevomelanocytes forming these lesions often do not demonstrate normal melanocytic differentiation and hence the term nevomelanocytes. The extent of melanocytic proliferation, spectrum and type of differentiation, location of cells, and age of the lesion all may influence clinical and histopathologic features.

The Melanocyte is a melanin-producing cell in the skin, that determines its color. Color is determined by the activity of the melanocytes. Melanin production takes place in melanosomes (tiny sub-structures within the cell). Darkly pigmented skin have melanosomes that contain more melananin.

Melanosomes are a network of microtubules that rearrange themselves within the cell in response to external factors such as ultraviolet rays. Melanosomes usually cluster together near the center of the cell but can rapidly redistribute themselves to the ends of dendritic (tooth-like) processes projecting from the cell. Each melanocyte supplies melanin to approximately 30 nearby keratinocytes via its dendrites along microtubules.

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.

Skin Moles Causes: There has been a continual debate as to the origin of skin moles. Although many theories have been proposed and some supporting data are available, the critical events leading to mole development remain a mystery. A number of hypotheses have been proposed. These include:
(1) transformation from epidermal melanocytes and subsequent deposition/migration into the dermis. Evidence for this hypothesis includes the demonstration of basement membrane around nevomelanocytes in the dermis based on routine, ultrastructural, and immunohistologic features, suggesting structural contiguity of dermal nevomelanocytes with epidermis. These studies would suggest that nevomelanocytes extend down from the epidermis along with the basement membrane.
(2) dual origin, i.e., nevomelanocytes in the epidermis and upper dermis being derived from epidermal melanocytes, and nevomelanocytes in the lower dermis being derived from Schwann cells of nerves. Evidence for this hypothesis is based on differences in differentiation of nevomelanocytes. This includes positive staining by a monoclonal antibody to the Schwann cell–associated antigen for nevomelanocytes in the lower dermis and negative staining for nevomelanocytes in the epidermis and upper and middle dermis. Moreover, nevomelanocytes in the epidermis and papillary dermis Typically resemble epithelioid cells, aggregate in nests, demonstrate tyrosinase activity but not cholinesterase activity, stain weakly for neuron-specific enolase, and contain melanin. Nevomelanocytes in the deep dermis tend to resemble fibroblasts or Schwann cells or form concentrically arranged and loosely layered structures becoming skin molesc corpuscles that resemble Meissner corpuscles, are usually disposed as single cells, demonstrate minimal tyrosinase activity, have abundant cholinesterase activity, and Typically stain positively for neuron-specific enolase. This hypothesis would suggest that the phenotypic differences in the nevomelanocytes are due to different origins (melanocytes and Schwann cells).
(3) hamartomatous change affecting many cell types. Evidence for this hypothesis includes changes in the associated epidermis, including lentiginous, seborrheic, or epidermal nevus type patterns, and aberrations of appendageal and neurovascular structures, particularly in congenital skin moles. These findings reinforce the notion that skin moles are benign hamartomas involving multiple tissue elements. The fourth hypothesis is based on the existence of defective melanoblasts that may lead to defective differentiation. Neural crest–derived melanoblasts migrate to the dermis and basal layer of the epidermis before 40 days of estimated gestational age. These cells are thought to take up residence in the epidermis and/or superficial dermis (or the deep dermis, panniculus, and adnexal structures in the case of congenital skin moles). Melanocytic “precursor” cells have been shown to be present in adult human skin. Theoretically, these cells could aberrantly proliferate and differentiate, giving rise to melanocytic neoplasms. Depending on the defect, timing, and local tissue influences, a variety of different melanocytic neoplasias could be created.
(4) benign neoplastic proliferation originating from a defect in melanoblast/neural crest cells.
This fourth hypothesis is supported by data showing that human acquired skin moles are clonal.

Typical acquired skin moles have not been followed systematically from their progression to regression. Therefore, dynamic evolution of acquired skin moles must be suggested from static information or short-term follow-up studies. It has been stated that during the early years of life, virtually all skin moles are composed primarily of junctional moles, that nevomelanocytes in these junctional moles eventually push their way to the dermis and finally lose their epidermal contact as they continue to grow into the dermis and become intradermal skin moles, and that in the intermediate stage of this process there are junctional moles in the epidermis and sheets and nests of nevomelanocytes in the dermis (i.e., compound skin moles). This argument suggests that because skin moles in adults are primarily of the dermal type and because skin moles in children are primarily of the junctional type, skin moles evolve by a process of “dropping down” of nevus cells from the epidermis into the dermis. The precise nature of the “dropping down” process has not been defined. It is likely that acquired skin moles evolve through a life cycle, first becoming apparent after infancy in the vast majority of cases, peaking in number during the second and third decades of life, and then disappearing by the seventh to ninth decades. Regression of skin moles is believed to occur by degeneration. The formation of degenerative structures in aging skin moles suggests an end stage in differentiation and not a source of origin of intraepidermal skin moles. Transepidermal elimination of nevomelanocytes rarely occurs. Rarely, nevomelanocytes have been documented to show spontaneous disappearance. Skin moles also may involute during the course of inflammatory halo depigmentation (halo moles). There may be relatively sudden changes in skin moles that are unrelated to cancerous transformation. Any single mole that is noted to suddenly change independently should be a cause for concern. Causes of sudden changes in a mole (color, surface, or size, with or without pain, itching, ulceration, or bleeding) over days or weeks include cystic dilatation of a hair follicle, epidermal cyst formation, folliculitis, abscess formation, trauma, hemorrhage, and, in the case of a pedunculated mole, strangulation and thrombosis. These benign causes of sudden change may require close observation until resolution occurs over the course of 7 to 10 days (in the case of trauma or inflammation) or histopathologic examination. Cases have been described of the eruptive appearance of skin moles after blistering skin disease, immunosuppression, or chemotherapy. The vast majority of acquired skin moles are harmless, growing in proportion to body growth, with physiologic spurts of enlargement during early childhood and puberty.
A cancerous mole risk appears to be related to the number and size of skin moles; patients with numerous skin moles, atypical skin moles, and a personal or family history of a cancerous mole should be considered for periodic surveillance examinations.

Typical acquired skin moles develop after birth, slowly enlarge symmetrically, stabilize, and persist or regress later in life. The majority of Typical acquired skin moles appear to develop during the second and third decades of life, although some lesions may appear in the first 6 to 12 months of life.
A number of studies have measured the number of typical acquired skin moles in different age groups. The average number of skin moles per person peaked at 43 for males and 27 for females during the second and third decades, respectively, and decreased to very few in the sixth and seventh decades. A similar age-related prevalence rate for skin moles has also been documented. A difference in frequency distribution of skin moles according to gender is not clear, although most series show a close to equal prevalence in males and females. The prevalence of skin moles varies according to race. In blacks, the overall prevalence of skin moles (regardless of size) tends to be higher in those with lighter skin versus those with darker skin. When prepubertal whites were examined for skin moles, a significant association for excess skin moles was documented for pale skin, blue or green eyes, blond or light-brown hair, and a tendency to sunburn, but not a tendency to freckle. Other studies show variable relationships to these same parameters. Environmental exposure to UV light appears to be a critical exacerbating factor for the development of skin moles. Mole density has been shown to increase with increasing sun intensity of UV light. Further, the use of UV blocking sunscreens has been shown to decrease the number of new moles in children. Genetics plays a role in mole development. There is evidence that the size, frequency, and distribution patterns of acquired skin moles tend to aggregate in families. This observation is well documented for atypical skin moles in the setting of familial cutaneous melanoma and congenital skin moles.

Moles are the most common lesions of the skin, occurring in all people at an average of 20 skin moles per person. As this is a common and noticeable lesion, and as the cancerous mole develops from the benign mole in the majority if not all instances, it is obvious that the management of skin moles is of great concern. Fortunately, only about one in every million skin moles becomes cancerous. The removal of skin moles has been greatly influenced by traditional teaching based on little, if any, scientific evidence. For example, trauma, acute or chronic, either accidentally or surgically produced, has been blamed for the stimulation of cancerous change in benign skin moles. There is no documented evidence that a previously treated microscopically proved benign mole has become cancerous following trauma of any type. In fact, the evidence that is available concerning the changes that occur in skin moles following partial removal and electrodesiccation with histological observation before and after tends to show that cancerous transformation does not occur.

Also, incisional methods of biopsy of pigmented lesions suspected of being cancerous moles have been considered hazardous because of the general belief that cutting into them increases the tendency to lympatic or hematagenous spread of cancerous cells. Again, there is no documented statistical proof that this occurs. Even a limited excision (that is, an excisional biopsy) of a cancerous lesion does often pass through cancer-bearing tissue (as is sometimes proved by local recurrences
of cancerous moles) and, if the theoretical objection to an incisional biopsy exists, then it should also apply to limited local excisional biopsy. In these circumstances, shave biopsy and electrodessication might be a preferable method of
partial biopsy because of the resultant sealing off of lymphatic and blood vessels. Also, there is no evidence that the inflammation or ulceration of a moles cancer resulting from trauma accelerates the growth of the lesion.

There are four indications for the removal of skin moles. First, the possibility of cancerous change occurring in a mole sometime in the future (a pre-cancerous active junctional mole) and removal is prophylactic as well as diagnostic; second, a suspected cancerous change already present, and removal is again diagnostic and therapeutic; third, cosmetic reasons; fourth, functional and anatomical changes occurring in a mole. The latter reasons, including irritation, trauma and infection, do not predispose skin moles to cancerous change, but removal is often advisable because of the associated nuisance and discomfort. This is particularly true with skin moles in certain areas that are recurrently or chronically subjected to these changes, such as the intertriginous areas, the hairy areas and pressure points under articles of clothing. Hairy skin moles can also be subjected to painful folliculitis, which is often a recurrent and annoying problem.

The method of removal of skin moles not only depends upon the indication for removal, but also the size, the clinical and morphological type, the location and the age of the patient. Even in the best circumstances of clinical evaluation of skin moles by experts, it is very evident that clinical acumen is not sufficient, and pathological examination of all treated skin moles is mandatory. In either of the first two categories, there is a possibility of cancerous or pre-cancerous change occurring; and complete removal or destruction of the mole is therefore essential. Any method of removal may be adopted whereby an adequate biopsy specimen is obtained and the residual mole cells completely removed or destroyed at the time or in the immediate future. Usually, if the lesion is not too large, simple elliptical excision with primary closure of the wound is the removal of choice.

In contradistinction, removal of skin moles for cosmetic or functional reasons does not always necessitate complete removal or destruction of all mole cells. Very often, the best result is produced by shaving off the mole flush with the skin and
then gently electrodesiccating the base. However, many physicians assume that, because the mole has been removed for cosmetic or functional purposes, electrodesiccating or other similar removal of physical type is always the method of choice. Possibly because of a lack of training or inclination, surgical excision is often neglected when it is the best form of removal irrespective of the type of mole or the reason for removal. The morphology of benign skin moles influences the choice of method of removal. A good example is the blue nevus, in which the mole cells are located deep in the dermis and, therefore, a pitted scar is left if the lesion is removed by shave excision and electrodesiccation. It is sometimes difficult to differentiate blue nevus clinically from a cancerous mole, and excisional biopsy is the best form of removal.

The hairy pigmented mole is another example of how gross structure can influence the method of removal. Even though hairs can first be removed by electrolysis and then later the residual lesion removed by shave excision and electrodesiccation
(or comparable methods), it is often simpler to excise the lesion in the first place, thereby producing an equally good cosmetic result. In order to carry out partial shave excision and electrodesiccation and achieve the best result, a lesion should usually have elevation to it; and flat skin moles therefore often lend themselves far better to simple excisional biopsy.

The size of skin moles is a factor in the choice of treatment. Medium to large skin moles are a particular problem, and except for the precancerous active junctional type, are best removed by shave excision and electrodesiccation, or sometimes by piecemeal excisional procedure. Both methods produce a better cosmetic result than reconstructional operation and skin grafting. However, the latter method may be the only one available in the case of very large skin moles, such as the bathing trunk type.

Location of the mole can be a determining factor in the method of removal. Surgical excision of lesions on the back often produces a scar which spreads and is quite unsightly. The same lesion can be removed by shave excision and electrodesiccation with a resultant soft, pliable, smaller scar which does not stretch and usually improves with age. Shave excision and electrodesiccation is the removal of choice of skin moles on the eyebrow, as excisional surgery will remove the hair follicles, thereby reducing or even completely destroying part of the eyebrow. For similar reasons, large skin moles
on the scalp are better treated by shave excision and electrodesiccation.

The controversy regarding whether skin moles on the hands and feet and genitalia should be removed prophylactically still exists. The argument in favor of removal is based on information that shows that the majority, if not all, skin moles in these areas are of the true junctional type; and although the hands and feet only constitute 10.5 per cent of the body's
skin surface, nevertheless approximately 16.5 percent of moles cancers occur in these areas, and of these 80 per cent are on the feet.5"1 This point of view is countered by the various clinical studies showing that approximately one in every six persons has at least one mole on the palm or sole, and therefore prophylactic extirpation of such lesions would be physically impossible.

Subungual skin moles appear to be rare. In one investigation no skin moles were found in a thousand persons studied; but the subungual moles cancer does constitute 3.3 per cent of all moles cancers. Therefore, a subungual pigmented lesion, unless it is obviously due to a benign condition such as a wart or subungual hematoma, should always be excised because of the possibility of its being a cancerous mole.

All skin moles removed should be pathologically examined to determine the type of mole. Occasionally, clinical errors are made, and if the lesion proves to be a cancerous mole or a premalignant junctional mole, then the area can be re-excised widely without affecting the ultimate prognosis. Junctional changes are obviously not in themselves a reason for re-excision, as most skin moles, even those that are clinically obviously intradermal in nature, contain some junctional changes. It has been found, that usually within one year following partial excision and electrodesiccation of skin moles, there is increased junctional activity and pigment formation. Our work so far shows that these changes usually decrease after one year. The clinical importance of this is that sometimes pigment reforms at the site of removal, and that in time may get less or even disappear. If this recurrence of pigment is unsightly or unacceptable to the patient, it can again be removed by shave excision and electrodesiccation. The occurrence of this pigment is fairly common, and its presence should not be, in itself, a sign for wide surgical excision of the area. It occurs more commonly in younger persons and in the more darkly pigmented lesions, and again in lesions which pathologically prove to have a good
deal of junctional activity. To avoid recurrence of the pigmented lesions in such individuals, surgical elliptical excision is often the removal of choice rather than shave excision and electrodesiccation.

Partial removal of skin moles by shave excision and electrodesiccation (or similar methods), accompanied by pathological examination, is the removal of choice for certain benign skin moles, depending on morphologic features, size, and location. Active junctional skin moles and suspected cancerous moles should be removed in their entirety, preferably by excisional operation.