Benign Growths

Acrochordon

Acrochordons are better known by their common name of skin tag or fibroepithelial polyp. They are found universally throughout humankind. Probably every adult has at least one skin tag located somewhere across the surface of his or her skin. Except for a few loose associations with certain syndromes, skin tags have no clinical importance and are often ignored.

Clinical Findings: Skin tags can be found throughout the adult population. They have no sex or race predilection. They are completely benign skin growths that have no malignant potential. They are most commonly located in the axillae, on the neck, in the groin area, and on the eyelids but can be found in other locations. Skin tags are almost never seen in children. The finding of a skin tag in a child should lead one to perform a biopsy to rule out a basal cell carcinoma. Basal cell carcinoma syndrome has been well documented to manifest in children, and the basal cell carcinoma has been shown in this syndrome to mimic the appearance of skin tags. If one sees a skin tag in a child, performs a skin biopsy, and discovers it is a basal cell carcinoma, the patient should immediately be evaluated for the basal cell carcinoma syndrome.

Most skin tags are minute, 1 to 5 mm in length, with a skin-colored to slightly hyperpigmented appearance. They are pedunculated papules that appear as outpouchings of the skin. They are soft and nontender. Occasionally, larger skin tags are found with a thickened or a more sessile stalk. These larger skin tags may approach 1 to 1.5 cm in length with a 5-mm base. Most individuals have more than one skin tag, and some individuals are afflicted with hundreds of them.

On occasion, a patient presents with a painful, necrotic skin tag. This is most commonly caused by trauma to the skin tag or twisting of the base that results in strangulation of the blood supply and subsequent necrosis. In these cases, removal is advised. If the appearance or clinical history is not classic, the specimen should be sent for pathological evaluation.

Many investigations have looked at the association of skin tags and underlying medical disorders with conflicting and confusing results. Patients with multiple skin tags may be at a higher risk for glucose intolerance. Some studies have even suggested that patients with multiple skin tags are at a higher risk for colonic polyps, but this is still subject to debate.

Pathogenesis: The pathogenesis of skin tags is believed to be a localized overgrowth of fibroblasts within the dermis. They may be more common during pregnancy, and they have been shown to be increased in patients with increased weight. This has led some to implicate insulin-like growth factor-1 as a possible driver of skin tag formation. The initiating factor is not completely understood.

Histology: The overlying epidermis is essentially normal. The skin tag appears as an outgrowth of the skin. The dermis appears normal, and there is a minimal inflammatory infiltrate present, if any at all. Thrombosed or strangulated skin tags show necrosis of the dermis and epidermis and thrombosis of the superficial supplying blood vessels. There is no atypia present.

Treatment: No therapy is necessary for these extraordinarily common skin growths. They are mostly overlooked and not even mentioned on routine skin examination. The rare strangulated or thrombosed skin tag can be removed easily with a forceps and skin tag removal scissors after injection of a local anesthetic. If cosmetic removal is desired, it can easily be done by cleaning the skin with alcohol or chlorhexidine and removing individual skin tags with a forceps and skin tag removal scissors. Application of aluminum chloride after removal causes the superficial bleeding to stop.

Screening of individuals with skin tags for errors in glucose metabolism or for colonic polyps is controversial but should be performed if other findings in the review of systems or the clinical history and physical examination suggests one of these underlying disorders.

Becker's Nevus (Smooth Muscle Hamartoma)

Becker's nevi most commonly appear on the shoulder or upper limb girdle of prepubescent boys. It is a rather common benign condition that is seen in up to 0.5% of the male population. It is less commonly seen in females. Becker's nevi are acquired nevi. Most occur before 10 years of age. Becker's nevus is classified as a smooth muscle hamartoma. It does not contain melanocytic nevus cells and is not considered to be a melanocytic nevus. It was given its name by the dermatologist Samuel Becker, who first described this condition.

Clinical Findings: Becker's nevi begin as ill-defined, slightly hyperpigmented macules on the upper limb girdle. Over time (1 year, on average), the hyperpigmented region develops hypertrichosis, resulting in its characteristic appearance. Backer's nevi may occur anywhere on the human body, but by far the most common locations are on the shoulder, upper chest, and back. The area of hypertrichosis is limited to the underlying hyperpigmented area. The clinical significance of Becker's nevi is its differentiation from large congenital nevi and café-au-lait macules. Becker's nevi confer no increased risk for development of melanoma, and they are rarely associated with any underlying abnormalities. The most common underlying abnormality is unilateral hypoplasia of the breast, which has minimal clinical significance. Rarely, a patient with a Becker's nevus has underlying hypoplasia of bone and soft tissue, the cause of which is unknown. The differential diagnosis includes a giant congenital nevus and a café-au-lait macule. These two conditions should be easily differentiated from Baker's nevus, because they both are typically apparent at birth or soon thereafter, whereas Becker's nevi are typically acquired at about the age of 10 years.

The diagnosis is typically made on clinical findings, but a skin biopsy is sometime needed to confirm the diagnosis if the nevus is in an unusual anatomical location. The punch biopsy is the best method for obtaining tissue.

Histology: The biopsy specimen shows a smooth muscle hamartoma. Multiple smooth muscle fascicles are seen within the dermis. There is an increased ratio of terminal to vellus hairs and a lack of melanocytic nevus cells. The hyperpigmentation results from increased formation of pigmentation within the melanocytes of the stratum basalis. There is no increase in the number of melanocytes. Varying amounts of acanthosis and hyperkeratosis are seen.

Pathogenesis: The pathogenesis of Becker's nevus is unclear. It is believed to be caused by the dermal presence of hamartomatous smooth muscle tissue. Research has shown that the tissue in Becker's nevi has an increased number of androgen receptors. It is thought that increased androgen levels at puberty interact with the excessive androgen receptors and cause the clinical findings.

Becker's nevus is the most common type of smooth muscle hamartoma in the skin. Smooth muscle hamartomas by themselves are rarely found within the skin. Non-Becker's smooth muscle hamartomas are usually present at birth or soon thereafter and manifest as a small, flesh-colored plaque located anywhere on the body. All smooth muscle hamartomas may at some point exhibit the pseudo-Darier's sign. To clinically elicit this sign, one gently rubs the smooth muscle hamartoma; the lesion may fasciculate due to smooth muscle activity, or the region may develop an urticarial appearance. This sign has nothing to do with histamine release; rather, it is caused by a neurally mediated contraction of the underlying hamartomatous smooth muscle tissue.

Treatment: No therapy is required. Surgical excision is likely to produce a mutilating scar unless the nevus is extraordinarily small. The hypertrichosis can be treated for cosmetic purposes with any of a multitude of therapies including laser removal, shaving, and electrolysis. Most patients prefer to not treat the area.

Dermatofibroma (Sclerosing Hemangioma)

Dermatofibromas are among the most common types of benign skin growths. Usually, they occur on the extremities, with a predilection for the legs. There is some debate as to whether this is a true neoplasm or an inflammatory reaction.

Clinical Findings: Dermatofibromas are seen almost exclusively in adults, and females tend to be afflicted slightly more often than males. There is no race predilection. Dermatofibromas can range in diameter from 2 mm to 2 cm. They are round or oval. Most often they are solitary, but numerous dermatofibromas may be present in an individual. Dermatofibromas are usually small (4-5 mm), firm, red to slightly purple papules that dimple with lateral pressure. This “dimple sign” is often used clinically to differentiate dermatofibromas from other growths. There are many variations of dermatofibromas clinically. Elevated dome-shaped papules or plaques may be seen. The surface may or may not have a slight amount of scale, and occasionally there is an appearance of hyperpigmentation. On the lower legs of females, they are often excoriated as a result of shaving, and this is often the reason the patient presents for evaluation. Dermatofibromas are most frequently asymptomatic, but they can be slightly pruritic.

If dermatofibromas are numerous and located in many areas of the body, the clinician should consider the association with an underlying immunodeficiency state. There have been reports of multiple eruptive dermatofibromas in patients with systemic lupus erythematosus, human immunodeficiency virus infection, and other immunosuppressive states. The dermatofibromas in these patients have been shown to contain more mast cells.

The differential diagnosis of a dermatofibroma can be broad. If the dermatofibroma does not exhibit the dimple sign, the lesion is often biopsied to help differentiate it from melanocytic nevus, melanoma, basal cell carcinoma, dermatofibrosarcoma protuberans (DFSP), prurigo papules, and other epidermal and dermal tumors.

Histology: Dermatofibromas are made up of a collection of dermal spindle-shaped fibroblasts. Histiocytes and myofibroblasts are also found throughout the lesion. The synonym sclerosing hemangioma arises when numerous extravasated red blood cells are seen within the dermatofibroma. Characteristically, the overlying epidermis is acanthotic with broadening of the rete ridges. The rete ridges are slightly hyperpigmented, and this is sometimes referred to as “dirty feet” or “dirty fingers.” This finding explains the hyperpigmentation seen clinically.

Dermatofibromas stain positively for factor XIIIa and negatively for CD34. This is the opposite of the pattern seen in DFSP. Immunohistochemical staining also provides a marker that can be used to help distinguish the benign dermatofibroma (which stains with stromelysin-3) from the malignant DFSP (which does not). In contrast to DFSP, dermatofibromas do not infiltrate the underlying adipose tissue. Dermatofibromas can push down or displace the adipose tissue, but they never truly demonstrate an infiltrative pattern as does a DFSP. There are numerous histological variants of dermatofibromas.

Pathogenesis: The precipitating factor that initiates the formation of a dermatofibroma is thought to be superficial trauma, such as from a bug bite, which causes the fibrous tissue proliferation. The exact etiology is unknown.

Treatment: Most dermatofibromas are not treated in any manner. Complete elliptical excision with a minimal 1- to 2-mm margin is curative. The resulting scar may be more noticeable than the initial dermatofibroma. There is no evidence to support the routine removal of these common tumors to prevent malignant degeneration into a DFSP.

Eccrine Poroma

Eccrine poromas are the most common tumors in the poroma family of skin tumors. Other tumors in this family include the dermal ductal tumor, the poroid hidradenoma, and the hidroacanthoma. Eccrine porocarcinoma is the rare malignant counterpart to the eccrine poroma. Eccrine poromas develop from the appendageal structures of the skin. The all-encompassing term poroma is more accurate in that it appears that not all of these tumors are derived from eccrine structures. There is unconfirmed evidence that the cell of origin is actually apocrine. Other possibilities for the cell of origin include the sebaceous gland and the follicular epithelium.

Clinical Findings: Eccrine poromas are uncommon tumors of the skin. They occur equally in men and women and almost exclusively in the adult population. They are typically small tumors, ranging from 5 to 20 mm. They are most frequently found on the soles and palms. As many as 50% to 60% of these tumors have been found on the sole, but they have been described to occur in any skin location. Pain and bleeding are the two most common symptoms encountered. Eccrine poromas tend to have a vascular appearance and often manifest as a red or purplish papule or nodule. They are almost always solitary in nature, and they easily bleed when traumatized. On inspection, the eccrine poroma often has a slight, dell-like depression surrounding the tumor. This is more commonly seen on acral skin. This dell, when seen by the perceptive clinician, often leads to a differential diagnosis that includes an eccrine poroma. There is nothing clinically that can be used with certainty to make the diagnosis. The differential diagnosis includes vascular tumors, metastatic lesions (particularly the vascular renal cell carcinoma metastasis), pyogenic granuloma, and melanoma, because some eccrine poromas exhibit pigmentation. The diagnosis is made by histological examination after biopsy.

Histology: Eccrine poromas show varying degrees of ductal differentiation. The tumor is well circumscribed and has characteristic features. The keratinocytes have been described as cuboidal. They tend to be small and have an increased nuclear to cytoplasmic volume. Necrosis is often seen in parts of the tumor. The ductal portions of the tumor are lined by an eosinophilic layer or cuticle. The stromal portions of the tumor are rich in vascular components. This vascular element imparts the red appearance to the tumor. Eccrine poromas can be histologically classified as other members of the poroma family of tumors, based on their location in the skin. As an example, the hidroacanthoma, a member of this family, is defined as an eccrine poroma that is entirely located in the epidermis.

The eccrine porocarcinoma is very uncommon; histologically, it is a tumor that is poorly circumscribed and often found in conjunction with an eccrine poroma. Cells with multiple large nuclei and multiple mitoses help make the diagnosis. Eccrine porocarcinomas can mimic metastatic adenocarcinomas, and immunohistochemical staining is required to make certain of the diagnosis.

Treatment: Although they are benign tumors, eccrine poromas often are located on the sole or palm and require removal from a functional standpoint. Surgical excision with a small (1-2 mm), conservative margin is curative. The recurrence rate is very low after surgical excision. Electrodesiccation and curettage has been used successfully. Eccrine porocarcinomas require surgical excision and close clinical follow-up. Chemotherapy is reserved for cases of metastatic disease. The role of sentinel lymph node sampling in these tumors has yet to be defined.

Eccrine Spiradenoma

Eccrine spiradenomas are uncommon benign tumors of the skin. Most often they are solitary, but they can occur in conjunction with cylindromas in the Brooke-Spiegler syndrome. They can occur in any location on the human body but are most commonly found on the head and neck. The next most common region is the ventral trunk. These tumors are uncommon on the extremities. Spiradenomas tend to appear between the ages of 15 and 40 years, although they have been reported to occur at any age. Malignant degeneration is extremely rare, but if it does occur, it is often fatal.

Clinical Findings: A spiradenoma usually manifests as a solitary dermal nodule or papule ranging from 5 to 20 mm in diameter. The average size is approximately 10 mm. They are typically seated deeply in the dermis and can be very painful to light touch. The tumors grow very slowly, and except for the pain can go unnoticed for some time. The pain tends to have a waxing and waning course, and it is more often than not the reason the patient seeks medical advice. The overlying epidermis is almost always normal. The dermal nodule sometimes takes on a purple or bluish coloration. Although they are most commonly solitary, multiple spiradenomas may be seen in association with multiple cylindromas in Brooke-Spiegler syndrome.

Brooke-Spiegler syndrome is an autosomal dominant inherited skin condition caused by a genetic defect in the CYLD gene. This syndrome is characterized by multiple cylindromas, spiradenomas, and trichoepitheliomas. The tumors usually begin in the third decade of life and increase in number and size throughout the patient's life. The CYLD gene encodes a tumor suppressor protein and is an important downregulator of the nuclear factor NF-κB pathway. The clinical phenotype varies depending on the type of mutation in this gene. Patients with familial cylindromatosis also have defects in this gene. The gene has been localized to the long arm of chromosome 16.

The eccrine spiradenoma is considered to be one of the group of unique tumors that can cause painful dermal nodules. This group also includes angiolipomas, neuromas, glomus tumors, and leiomyomas. This group of tumors makes up the differential diagnosis when evaluating these painful nodules. If the nodule is asymptomatic, lipoma and other adnexal tumors would also be considered in the differential diagnosis.

The exact cell type from which the spiradenomas are derived is still undetermined. They were originally believed to arise from eccrine tissue, but increasing evidence is pointing to a derivation from apocrine tissue.

Histology: The histological hallmark of an eccrine spiradenoma is the appearance of large nests of basophilic cells in the dermis. There are no epidermal changes, and the multilobulated tumors do not connect with the epidermis. This gives rise to the term “blue balls in the dermis.” The tumor is composed of two unique cell types. Large, pale cells predominate, with surrounding aggregates of smaller basophilic cells that contain hyperchromatic nuclei. The tumor is well circumscribed and is surrounded by a fibrous capsule.

Treatment: Surgical excision is curative. Surgical removal with carbon dioxide laser ablation has also been found to be highly successful. Because of the number and size of the tumors in patients with the Brooke-Spiegler syndrome, a multidisciplinary approach is often taken. Plastic surgeons are often the primary physicians removing these tumors.

Eccrine Syringoma

Eccrine syringomas are extremely common benign skin growths. They are most often found on the lower eyelids and malar cheek regions of adults. These small tumors are of no clinical significance and are routinely ignored in clinical practice.

Clinical Findings: Eccrine syringomas are some of the most common benign skin tumors to affect humankind. They are believed to be more common in women than in men. They typically manifest in adulthood as flesh-colored, small (2-4 mm) papules on the lower eyelids or upper cheek regions. They are usually multiple and symmetric. Some have a slight yellow or tan hue. Other areas of the body on which syringomas are seen include the upper eyelids, neck, and chest. They have been reported to occur on any region of the body.

Plaque-like syringomas have been reported to occur on the forehead, and they have the appearance of a flesh-colored to slightly yellow, broad, flat plaque with minimal to no surface change. They can be quite large, up to 4 to 5 cm in diameter. They are essentially asymptomatic, but occasionally a patient complains of slight intermittent itching or of an increase in size with strenuous physical activity. This is possibly explained by the eccrine nature of the tumors: Under conditions of activity, an increase in sweating causes the tumors to transiently appear to enlarge. There are specific variants seen in patients with diabetes mellitus and in those with Down syndrome. A form of eruptive syringoma has been described that typically afflicts the anterior trunk and the penile shaft. Linear syringomas have been reported to occur on a unilateral limb, and these have been termed unilateral linear nevoidal syringomas .

The clinical differential diagnosis of eccrine syringomas is relatively limited when the clinician encounters symmetric small papules on the lower eyelids. The differential diagnosis for a solitary syringoma is broad and includes other adnexal tumors as well as basal cell carcinoma. The most difficulty arises when reviewing the histological features of a syringoma that has been biopsied in a superficial manner. If the pathologist is not given a thick enough specimen, the eccrine syringoma can mimic a microcystic adnexal carcinoma. These two tumors, one benign and the other malignant, can have very similar histological features in the superficial dermis. In some cases, it is only with a full-thickness biopsy that a pathologist can confidently differentiate the two tumors.

Histology: The overlying epidermis is normal. The tumor is based within the dermis and is sharply circumscribed. The syringoma typically does not penetrate deeper than the upper third of the dermis. Clusters of cells with a pale cytoplasm are found throughout the tumor. A background of sclerotic stromal tissue is always appreciated. A characteristic finding is the “tadpole” sign. The tadpole- or comma-shaped, dilated ductal eccrine gland apparatus is pathognomonic for eccrine syringoma. Clear cell variants are associated with diabetes mellitus. A microcystic adnexal carcinoma is poorly circumscribed, is asymmetric, and infiltrates into the underlying subcutis.

Pathogenesis: Eccrine syringomas are believed to be an overgrowth of the eccrine sweat ductal apparatus. Researchers have proposed that this proliferation is caused by an inflammatory response to an as yet undetermined antigen. The precise pathogenesis of eccrine syringomas is unclear. Familial patterns suggest a genetic predisposition, but most patients do not have a family history to support genetic transmission.

Treatment: No treatment is necessary. If one wishes to pursue therapy, it should be done with caution, because treatment experiences are anecdotal, and scarring may have a worse appearance than the syringoma itself. Electrocautery, light cryotherapy, chemical peels, laser resurfacing, dermabrasion, and excision have been reported with variable results.

Ephelides and Lentigines

Ephelides, also known as freckles, are common benign findings. They typically manifest in childhood in fair-skinned individuals, especially those with red or blonde hair color. Ephelides tend to be passed down from generation to generation in an autosomal dominant inheritance pattern.

Lentigines are sun-induced proliferations of melanocytes. They tend to occur in older people, but they may be seen in individuals at a young age after repetitive sun exposure. They can be almost impossible to differentiate from ephelides. Solar lentigines have many synonyms, including sun spots, liver spots, and lentigo senilis.

Clinical Findings: Ephelides occur at a very young age and tend to show an autosomal dominant inheritance pattern. They are accentuated in sun-exposed regions, particularly the head, neck, and forearms. Exposure to the sun or other ultraviolet source causes the ephelides to become darker and clinically more noticeable. They do not occur within the oral mucosa. They are usually uniform in coloration but can have many different sizes and shapes. Some are round or oval; others are angulated or have a bizarre shape. Their color is usually a uniform light to dark brown; they are never black. They have no malignant potential. Patients with multiple ephelides may have a higher risk for skin cancer, because their presence may be an indication of increased exposure to ultraviolet radiation. The differential diagnosis is usually very narrow and includes lentigines and common acquired nevi. The clinical location, age at onset, family history, and skin type usually make the diagnosis straightforward. The difficulty can occur when trying to differentiate a solitary lentigo from an ephelide in an adult patient.

Solar lentigines most often arise in the adult population and are distributed evenly among males and females. They can occur in anyone but are much more common in light-skinned persons. The number of lentigines typically increases with the age of the patient. Lentigines are induced by ultraviolet radiation, the most common source being chronic sun exposure. Lentigines tend to get darker with ultraviolet light exposure and lighten over time when removed from the exposure. Unlike ephelides, they never completely fade away. They are clinically highly uniform in color and size within an individual patient. They can be small (1-5 mm), but some are much larger (2-3 cm in diameter). They are most commonly located in sun-exposed areas but in some syndromes can be located anywhere on the human body, including the mucosal regions. Over time, some lentigines merge together to form rather large lentigines.

There are some important variants of lentigines. Lentigo simplex and the ink spot lentigo are two very common versions. Lentigo simplex is believed to occur at any age and to have no or minimal relationship to sun exposure. The lesions are found anywhere on the body. Ink spot lentigines are variants of lentigo simplex that are differentiated by their characteristic dark brown to almost black coloration. Under dermatoscopic evaluation, they have a characteristic uniform pigment network, with accentuation of pigment in the rete ridge regions. They are so named because they have the appearance of a tiny drop of dark ink dropped on the skin. Neither of these two forms of lentigines has malignant potential.

One of the more important and unique variants of lentigines are the psoralen + ultraviolet A light (PUVA) lentigines. PUVA lentigines are iatrogenic in nature and occur after medical therapy with PUVA treatment. Patients who have undergone long-term therapy with PUVA have a high risk of developing PUVA lentigines. These lentigines are darkly pigmented macules that occur across the entire body except in the areas that were not exposed to the PUVA therapy. More than half of patients who have undergone prolonged PUVA treatment will develop PUVA lentigines. They are more common in patients with fair skin types and rarely occur in darker-skinned individuals. The lentigines induced by PUVA therapy are permanent and can have disastrous cosmetic consequences. Like all patients undergoing ultraviolet phototherapy, these patients must be routinely monitored for their entire lives, because they are at increased risk for melanoma and non-melanoma skin cancer due to their chronic use of PUVA treatment.

Patients with Peutz-Jeghers syndrome have clinical findings of multiple lentigines of the oral mucosa and lips and of the hands. These patients are at increased risk for gastrointestinal carcinomas, particularly colon cancer. Peutz-Jeghers syndrome is inherited in an autosomal dominant fashion and is caused by a defect in the STK11/LKB1 tumor suppressor gene.

LEOPARD syndrome is another of the well-described genetic syndromes associated with lentigines. This syndrome is composed of l entigines, e lectrocardiographic abnormalities, o cular hypertelorism, p ulmonary stenosis, a bnormal genitalia, r etardation of growth, and d eafness. It is caused by a genetic mutation in PTPN11 , which encodes a tyrosine phosphatase protein.

Histology: Histopathological evaluation is one method to differentiate a lentigo from an ephelide. This is rarely done. The most common use of histology is to differentiate the benign lentigo from its malignant counterpart, lentigo maligna (melanoma in situ).

On histopathologic evaluation, ephelides show no change in the epidermis. There is no increase in the number of melanocytes. The only finding is an increase in the amount of melanin and an increased rate of transfer of melanosomes from melanocytes to keratinocytes.

Lentigines, on the other hand, show an increased number of melanocytes within the area of involvement. The hyperpigmentation is obvious along the club-like configuration of the rete ridges. The increase in the number of melanocytes is not associated with any nesting of those melanocytes, as is seen in melanocytic nevi. In solar lentigines, the dermis often shows signs of chronic sun damage, with a thinning of the dermis and solar elastosis. The epidermis is also thinned in some cases.

Lentigo maligna shows many more melanocytes, some large and bizarre appearing. There is pagetoid spread of the melanocytes and an asymmetry to the lesion. Lentigo simplex has also been shown to lack defects in the BRAF gene, in contrast to melanoma, and this may be one way to differentiate the two.

Pathogenesis: Ephelides are thought to be genetically inherited, most likely in a dominant pattern. They become more prominent with sun exposure and fade during times with less exposure to ultraviolet radiation. The increase in pigment is caused by an increase in the production of melanin and an increase in the transfer of melanosomes from melanocytes to keratinocytes. There is no increase in the number of melanocytes in ephelides. The exact reason for this has not been determined.

Lentigines are caused by an increased proliferation of melanocytes locally within the skin. The cause of this proliferation is most likely ultraviolet light in the case of solar lentigines. In the case of lentigo simplex, the cause is unknown. The increased number of melanocytes ultimately leads to an increase in the amount of melanin produced, resulting in the overlying hyperpigmentation.

The cause of lentigines in some of the genetic disorders is probably the underlying genetic defect. The exact mechanism of how the various gene defects lead to an increase in lentigines is under investigation. A better understanding of how lentigines form in certain genetic syndromes may lead to discovery of the true pathogenesis of solar lentigines and lentigo simplex.

Treatment: No therapy is needed other than to recommend sun protection, sunscreen use, and routine skin examinations in the future. For cosmetic reasons, lentigines can be removed in a myriad of ways. Light cryotherapy is effective and easy to perform. This treatment can leave hypopigmented areas and should be used with caution in darker-skinned individuals. Many different chemical peels and dermabrasion techniques have been used to help decrease the appearance of lentigines. With the proliferation of medical laser devices in dermatology, lasers with unique wavelengths have been developed to target the melanin in lentigines. These laser devices have shown promise in lightening and removing solar lentigines.

Epidermal Inclusion Cyst

Epidermal inclusion cysts are the most common benign cysts derived from the skin. They are also known as epidermoid cysts or follicular infundibular cysts. The name “sebaceous cyst” has been used to describe these cysts, although this is a misnomer, because epidermal inclusion cysts are not derived from sebaceous epithelium. The cysts can occur anywhere on the body except the palms, soles, glans, and vermilion border.

Clinical Findings: Most epidermal inclusion cysts are subcutaneous nodules that vary in size from 5 mm to more than 5 cm. They have no race predilection but are seen more commonly in men than in women. Onset most commonly occurs during the third decade of life. The nodules characteristically have an overlying central punctum. From this punctum, drainage of white, cheese-like material, which represents a buildup of macerated keratin debris, can occur. Most small epidermal inclusion cysts are asymptomatic, and they rarely cause a problem.

Larger epidermal inclusion cysts can become irritated and inflamed. If the inflammation is severe enough, the cyst wall ruptures. When the cyst contents enter the dermis, the keratin sets off a massive inflammatory reaction, which manifests clinically as edema, redness, and pain. Once this has occurred, patients often seek medical advice.

The main differential diagnosis for a ruptured epidermal inclusion cyst is a boil or furuncle. Ruptured epidermal inclusion cysts are almost never infected, although infection can occur within a long-standing ruptured cyst that has not been treated. The main differential diagnosis of an unruptured, noninflamed epidermal inclusion cyst is a pilar cyst. Pilar cysts do not have an overlying central punctum, and this is the easiest means of differentiating the two cyst types. Pilar cysts are also more common on the scalp. Milia are considered to be tiny epidermal inclusion cysts.

Histology: The epidermal inclusion cyst is a true cyst with an epithelial lining of stratified squamous epithelium and an associated granular cell layer. The central cavity is filled with keratin debris. The cyst is derived from follicular epithelium.

Pathogenesis: The epidermal inclusion cyst is derived from the infundibulum of the hair follicle. Epidermal inclusion cysts occur as the result of direct implantation of epidermis into the underlying dermis; from there, the epidermal component continues to grow into the cyst lining. Many researchers have looked at the roles of ultraviolet light and human papillomavirus infection in the etiology, but no definitive conclusions on either have been drawn.

Treatment: Small cysts that are asymptomatic do not need to be treated. One should advise patients not to manipulate or squeeze the cysts. Such trauma could cause rupture of the cyst wall and set off an inflammatory reaction. Small cysts can be cured by a complete elliptical excision, making sure to remove the entire cyst wall. If a small portion of the cyst wall is left behind, the cyst is likely to recur.

Inflamed cysts should be treated initially with an incision and drainage technique. The region is anesthetized and then incised with a no. 11 blade. The resulting cheesy-white macerated keratin debris is removed with lateral pressure, and a curette is used to break apart internal loculations. The drainage material has a pungent odor. The resulting cyst cavity can be packed or left open until the patient returns in 2 to 3 weeks for definitive removal of the cyst lining by excision. Intralesional triamcinolone is very effective in decreasing the inflammation and pain in these inflamed cysts. Long-standing cysts should be cultured and the patient given the appropriate antibiotic therapy based on the culture results.

Epidermal Nevus

Epidermal nevi are benign epidermal hamartomatous growths that most commonly occur as small plaques but can be widespread and can have associated systemic findings. Epidermal nevi have a tendency to follow the embryologic lines of Blaschko. The lines of Blaschko are well defined and follow a whorl-like pattern. The reason why these lesions follow Blashko's lines is not fully understood, but it is probably caused by an interruption of normal epidermal migration during embryogenesis.

Clinical Findings: The epidermal nevus typically manifests in childhood as a solitary linear plaque. Epidermal nevi do not have a race predilection, and they can be found equally in males and females. This type of nevus is not melanocytic in nature; rather, it is composed of a proliferation of keratinocytes. The nevus initially has a smooth surface and develops a mamillated or verrucal surface over time. Epidermal nevi appear to occur most commonly on the head and neck region but can occur anywhere. After puberty, the lesions do not change dramatically. Most are flesh colored to slightly hyperpigmented. If found on the scalp, an epidermal nevus can mimic a nevus sebaceus and can be associated with hair loss, but more commonly it does not cause alopecia.

The epidermal nevus is usually small and slightly linear. Some are large, encompassing the entire length of an extremity, and still others cover a large percentage of the body surface area. Rarely, there is intraoral mucosal involvement. These larger epidermal nevi are more likely to be associated with systemic findings, such as underlying bone abnormalities. The most common bony abnormality is shortening of the unilateral limb. The epidermal nevus syndrome is a rare disorder associated with a large or widespread epidermal nevus and many systemic findings.

The epidermal nevus syndrome is made up of a constellation of findings. These children often present with neurological deficits, including seizures, and developmental delay. They can have a multitude of bony abnormalities, cataracts, and glaucoma. The finding of a widespread epidermal nevus in an infant should alert the clinician to the possibility of this syndrome and the need for a multidisciplinary approach to patient care.

Pathogenesis: The epidermal nevus is a hamartomatous proliferation of the epidermal components. The exact cause is unknown. These lesions are believed to be caused by a developmental abnormality of the ectoderm. The epidermal nevus syndrome has not been shown to have any appreciable inheritance pattern and is believed to be sporadic in nature. The exact genetic defect is unknown; it is most likely a result of genetic mosaicism. The involvement of fibroblast growth factor has been studied, but no firm conclusions have been made. These lesions do not show any abnormalities of melanocytes.

Histology: The findings in this condition are all located within the epidermis. Significant acanthosis and hyperkeratosis, with papillomatosis, predominates. A variable degree of pigmentation is seen in the involved keratinocytes, but this is not a disorder of melanocytes, and the number of melanocytes is normal. The granular cell layer is expanded. Many unique histological variants of epidermal nevi have been described.

Treatment: Small, isolated epidermal nevi can be removed with shave removal technique. They have a high rate of recurrence with this technique, but recurrence may take many years. The advantages of this technique are that it is relatively easy, noninvasive, and quick, and it provides an opportunity to histopathologically evaluate the tissue for any evidence of epidermolytic hyperkeratosis. The disadvantage of shave removal is that it is appropriate only for small epidermal nevi. Cryotherapy with liquid nitrogen has been used successfully, but it may leave unsightly hypopigmentation in darker-skinned individuals and should be used with caution.

Complete surgical excision is curative for small epidermal nevi. However, it leaves a scar that may be more noticeable than the nevus was. Laser resurfacing, dermabrasion, and chemical peels have been used to help smooth out the appearance of epidermal nevi.

Fibrofolliculoma

Fibrofolliculomas are uncommon benign tumors of the skin. They are derived from the hair follicle epithelium and show a unique mantle differentiation. These tumors are uncommonly seen, but if they are seen in multiples, one needs to consider that they are a constellation of Birt-Hogg-Dubé syndrome.

Clinical Findings: These tumors, when seen, are often solitary skin growths on the head and neck. They are small (2-5 mm), flesh-colored to tan-yellow papules. They most commonly manifest in the third or fourth decade of life. They are asymptomatic and rarely, if ever, get inflamed or bleed spontaneously. On occasion, a small hair is seen emanating from the center of the lesion. The main differential diagnosis clinically includes compound nevus, basal cell carcinoma, fibrous papule, and other types of adnexal tumor. Definitive diagnosis is impossible without histological examination. Solitary fibrofolliculomas are usually found incidentally on routine skin examination. Some patients present with a slightly enlarging new papule, often expressing concern for or fear of skin cancer.

Multiple fibrofolliculomas are seen in association with Birt-Hogg-Dubé syndrome. This syndrome is caused by a genetic defect in the tumor suppressor gene, folliculin (FLCN) . This gene has been localized to the short arm of chromosome 17. Other cutaneous constellations of this autosomal dominantly inherited syndrome include trichodiscomas and skin tags. The most important aspect of diagnosing this syndrome early is to screen patients for the possibility of renal tumors, both benign and malignant. Renal oncocytomas are the most common malignant renal tumor seen in this syndrome. Another rare renal cancer, the chromophobe renal cell carcinoma, also may be seen. This very rare tumor is seen in a higher percentage of patients with Birt-Hogg-Dubé syndrome than in the general population. It has a less aggressive behavior than other forms of renal cell carcinoma. Patients with this syndrome are also at higher risk for spontaneous pneumothorax. Some believe that trichodiscomas are the same type of tumor as the fibrofolliculoma and that the difference in histological appearance is caused by sampling and processing artifact (i.e., the identical tumor processed at different tissue surface levels).

Pathogenesis: Fibrofolliculomas are believed to be derived from the upper part of the follicular epithelium. The tumors are thought to be hamartomatous processes that develop within the dermis. Mantle-like structures, as seen in sebaceous glands, are often present and may be the derivation of these tumors. Some authors even consider the manteloma (an extremely rare benign skin tumor) to be in the same spectrum of tumors as the fibrofolliculoma and the trichodiscoma.

Histology: The tumor surrounds a well-formed terminal hair shaft. The upper portion of the hair shaft is slightly dilated. Emanating from the central hair shaft epithelium are cords or epithelial strands that project into the surrounding dermis. These cords interconnect at various positions and form a weave-like pattern. Trichodiscomas do not contain a hair shaft; one sees a proliferation along a hair follicle of a fibrovascular stroma akin to an angiofibroma. It is postulated that these two tumors are indeed the same but appear to be two distinct tumors due to routine processing and sampling at various tissue plane levels.

Treatment: Solitary fibrofolliculomas can be removed completely with the shave removal technique. This gives excellent cosmetic results, and the tumors are unlikely to recur. Multiple tumors are more difficult to remove; laser resurfacing, dermabrasion, and chemical peeling have all been used with varying results. The recognition of multiple fibrofolliculomas or trichodiscomas necessitates screening for Birt-Hogg-Dubé syndrome.

Fibrous Papule

Fibrous papules are one of the most common benign skin growths encountered. They are often overlooked or ignored during routine skin examinations. The exact incidence is unknown, but they are believed to be extraordinarily common. These skin growths are most frequently found on the nose, but they can occur anywhere, especially on the face.

Clinical Findings: Fibrous papules are typically small, 0.5 to 5 mm in diameter. They are slightly oval and dome shaped with an overlying smooth surface. Most commonly, they are flesh colored to slightly hyperpigmented. Fibrous papules can also have a hypopigmented appearance. These benign tumors are almost entirely asymptomatic. On occasion, a patient notices a slight itching sensation; less frequently, a patient may describe spontaneous bleeding or bleeding after minor trauma. These growths are most often solitary in nature, but multiple fibrous papules have been reported. Fibrous papules most commonly occur in young adults, especially in the third to fifth decades of life. The most common location is the face, with the nose and chin the two areas most commonly involved.

Fibrous papules are considered to be angiofibromas. Multiple angiofibromas can be part of a constellation known as the tuberous sclerosis syndrome. The differential diagnosis in a teenager with multiple angiofibromas should always include tuberous sclerosis. However, solitary fibrous papules are extraordinarily common and should not cause one to look for an underlying syndrome such as tuberous sclerosis. Pearly penile papules are small, dome-shaped, 1- to 2-mm papules found along the corona of the glans. These pearly penile papules are histologically indistinguishable from fibrous papules and are also considered to be angiofibromas.

The differential diagnosis of a fibrous papule can be quite broad, and a biopsy is often required to differentiate the potential mimickers. The entities most commonly included in the differential diagnosis are common acquired melanocytic nevus and basal cell carcinoma. In these cases, a shave biopsy is required to make a firm diagnosis.

Histology: A fibrous papule is considered to be an angiofibroma. There are multiple histological variants of fibrous papules. The most commonly encountered fibrous papules are typically dome shaped and small (up to 5 mm in diameter), and they show a proliferation of fibroblasts with a stroma of fibrotic collagenized material. Dilated blood vessels are often found within the papules. An inflammatory infiltrate is frequently seen, but it is typically sparse. The combination of clinical findings with the typical histopathological findings solidifies the diagnosis.

Multiple histological variants have been described, including pleomorphic, pigmented, granular cell, hypercellular, and clear cell variants. These variants are believed to be much less common than the classic type of fibrous papule. They have been described in detail and are well accepted and recognized histopathological variations.

Pathogenesis: Fibrous papules are believed to be a benign proliferation of fibroblasts and blood vessels in a collagen-filled stroma. Immunohistochemical staining has shown that the dermal dendrocyte is the most likely precursor cell to the abnormal fibroblasts seen in fibrous papules. The underlying cause has yet to be determined. The multiple angiofibromas of tuberous sclerosis are directly related to an underlying defect in the tumor suppressor gene, tuburin (TSC2) . Patients with tuberous sclerosis also have angiofibromas in a periungual location, as well as hundreds to thousands of angiofibromas located symmetrically on the face and nose.

Treatment: No treatment is necessary, although a small shave biopsy is often all that is required to remove the fibrous papule with an excellent cosmetic result. Most fibrous papules are removed because they are mistaken for basal cell carcinomas or for relief of some underlying irritation, such as itching or bleeding.