Section J: Benign Neoplasms

PATIENT STORY

A 55-year-old man requests removal of multiple skin tags around his neck. He is overweight and has diabetes and acanthosis nigricans. Although some of his skin tags occasionally get caught on his clothing, he just doesn't like the way they look. The patient chose to have many of them removed by the snip excision method.

INTRODUCTION

Skin tags (acrochordons) are flesh-colored, pedunculated lesions that tend to occur in areas of skin folds, especially around the neck and in the axillae.

SYNONYMS

• Acrochordons, fibroepithelial polyps.

EPIDEMIOLOGY

• In an unselected population study, skin tags were found in 46% of adults, particularly in persons who were obese.¹

• Skin tags increase in frequency through the fifth decade of life so that as many as 59% of individuals have them by the time they are 70 years old; however, the increase slows after age 50 years.¹

ETIOLOGY AND PATHOPHYSIOLOGY

• Three types of skin tags are described¹:

  • Small, furrowed papules of approximately 1 to 2 mm in width and height, located mostly on the neck and the axillae (Figure 163-1).

  • Single or multiple filiform lesions of approximately 2 mm in width and 5 mm in length occurring elsewhere on the body (Figure 163-2).

  • Large, pedunculated tumor or nevoid, baglike, soft fibromas that occur on the lower part of the trunk (Figure 163-3).

• Etiology is unknown, but it is theorized that skin tags occur in localized areas with a paucity of elastic tissue resulting in sessile or atrophic lesions. In addition, hormone imbalances appear to facilitate their development (e.g., high levels of estrogen and progesterone seen during pregnancy) and other factors including epidermal growth factor, tissue growth factor-α, and infection have been implicated as cofactors.

• Mast cells were found in higher density in skin tags than in normal skin in one study, suggesting a possible role in promoting fibrosis and skin tag development.²

• Acrochordons also appear to be associated with impaired carbohydrate metabolism and diabetes³ (see Figure 163-1), as well as colon polyps (odds ratio [OR] 7.07).⁴

• Very rarely, neoplasms are found at the base of skin tags. In a study of consecutive cutaneous pathology reports, 5 of 1335 clinically diagnosed fibroepithelial polyp specimens were malignant (i.e., 4 were basal cell carcinomas and 1 was squamous cell carcinoma in situ).⁵ There is a large selection bias in this study because most skin tags are not sent to the pathologist (nor should they be sent unless there is a suspicious feature).

DIAGNOSIS

CLINICAL FEATURES

• Small, soft, usually pedunculated lesions.

• Skin colored or hyperpigmented.

• Most vary in size from 2 to 5 mm, but larger ones do occur.

• Usually asymptomatic, but can be pruritic or become painful and inflamed by catching on clothing or jewelry.

TYPICAL DISTRIBUTION

• Most typically seen on the neck and in the axillae (see Figure 163-1), but any skin fold may be affected. They are also seen on the trunk (see Figure 163-3), the abdomen, and the back.

BIOPSY

• Not usually indicated unless the diagnosis is not clear. Typical skin tags do not need to be sent to pathology upon removal. Skin tags, on histology, are characterized by acanthotic, flattened, or frondlike epithelium. A papillary-like dermis is composed of loosely arranged collagen fibers and dilated capillaries and lymphatic vessels.

DIFFERENTIAL DIAGNOSIS

Lesions that can be confused with skin tags include:

• Warts—Cutaneous neoplasm caused by papillomavirus. There are common warts, flat warts, plantar warts, and condyloma acuminatum. Filiform common warts resemble skin tags more than most other warts. The typical distribution of warts on the hands, feet, and genitalia helps to differentiate these from skin tags.

• Neurofibromas—These benign Schwann cell tumors are soft pedunculated masses (Figure 163-4). These can be solitary tumors in persons who do not have neurofibromatosis. It is relatively easy to differentiate these from skin tags in persons who do have neurofibromatosis.

• Nevi—Any small benign pedunculated nevus may resemble a skin tag, but usually their larger size, location, and pigment pattern differentiate them from skin tags. Epidermal hyperplasia in melanocytic nevi (also called keratotic melanocytic nevus [KMN]) may have overlying hyperplastic epidermis resembling skin tags. In a study of melanocytic nevi submitted for pathology over an 8-month period, 6% were KMN, most often located on the trunk (76%).⁶ Intradermal nevi can be pedunculated and sparsely pigmented, but they are usually larger than skin tags and are often found on the face.

MANAGEMENT

FIRST LINE

• Give the patient a choice between snip excisions and cryotherapy. Snip excisions are fast and provide immediate results. Cryotherapy is also rapid and does not cause bleeding in the office. The downside of cryotherapy is that it may take 2 weeks for the skin tags to fall off and there is no guarantee that 100% of them will fall off. Both methods are well tolerated. Some patients may fear the snip excision more than the freezing method; others may want to try both methods to see which one hurts least. Ultimately the best method is a matter of patient preference.

• Snip excision—Small lesions may be snipped with a sharp iris scissor with or without anesthesia (Figure 163-5). The advantage of this method is that it works immediately and is 100% effective. If there is any bleeding, aluminum chloride on a cotton-tipped applicator is applied for hemostasis. It is unnecessary to use anesthesia for the smallest skin tags unless the patient requests it. It helps to use 1% lidocaine with epinephrine injected with a 30-gauge needle under the skin tag when skin tags are large or have a wide base. This makes the snip painless and decreases the bleeding (especially if one waits for the epinephrine to take effect).

• Cryotherapy with liquid nitrogen can be applied directly to the skin tag with a spray from a cryogun or direct application with forceps or Cryo Tweezers. Cryo Tweezers are manufactured by Brymill, Inc. They have a large metal end to hold the cold longer (Figure 163-6). The Cryo Tweezers are usually less painful because the skin tag can be frozen without the spray freezing the skin around it. They are safer for skin tags on the eyelids than the spray method. This is a very efficient way to treat multiple skin tags (approximately 10–15 with a single dip into the liquid nitrogen). Standard forceps require redipping into the liquid nitrogen for every 1 to 2 skin tags. Although cryotherapy is easy to perform and some patients find it less painful, it is not uncommon for some of the skin tags to not fall off.

• Larger skin tags and fibromas may be removed with a snip or shave excision after injecting the base with 1% lidocaine and epinephrine.

• Most insurance companies will not pay for the cosmetic removal of skin tags.

• To avoid large healthcare costs, send only suspicious-looking skin tags to the pathologist.

SECOND LINE

• Ethyl chloride spray anesthesia has been described as one method to decrease pain during snip excision with microscissors and microforceps.⁷ The spray itself is somewhat uncomfortable and jarring when it hits the skin, and the effect lasts for a few seconds. It can also produce intoxication through inhalation. In our experience there is insufficient benefit to outweigh the risks, time, and costs of ethyl chloride. When anesthesia is needed, injectable lidocaine with epinephrine is most reliable.

• Cryotherapy using liquid nitrogen applied with a cotton-tipped applicator is an option in practices that do not have a cryogun or Cryo Tweezers.

• Cryotherapy with cryogens other than liquid nitrogen provides additional options. As these cryogens are not as cold as liquid nitrogen, they are considered second-line therapy.

• An adhesive patch that applies pressure to the base of a skin tag was found effective in 65% of skin tags in one case series.⁸

• Electrodesiccation with or without anesthesia works for very tiny skin tags too small to grab with the forceps.

FOLLOW-UP

• Follow-up is not usually necessary.

PATIENT EDUCATION

• Advise patients that these are benign growths that can be removed if irritation occurs or for cosmetic purposes. Patients who are overweight should be encouraged to lose weight for their general health and to avoid new skin tags.

REFERENCES

PATIENT STORY

An elderly woman noted growth of a lesion on her chest (Figure 164-1). She was afraid that it might be melanoma. Her family physician recognized the typical features of a seborrheic keratosis (SK) (stuck on with visible horn cysts) and attempted to reassure her. Dermoscopy was performed, and the features were typical of an SK; the physician was able to convince the patient to not have a biopsy (Figure 164-2). The black comedo-like openings and white milia-like cysts are typical of an SK and can be seen with the naked eye in this case, and even better with a dermatoscope.

INTRODUCTION

• An SK is a benign skin tumor and a form of localized hyperpigmentation as a result of epidermal alteration; it develops from the proliferation of epidermal cells, although the cause is unknown.

SYNONYMS

Senile keratoses, age spots.

EPIDEMIOLOGY

• Most common benign tumor in older individuals; frequency increases with age.

• In a study of individuals older than age 64 years in North Carolina, 88% had at least one SK. Ten or more SKs were found in 61% of the black men and women, 38% of the white women, and 54% of the white men in the study.¹

• In an Australian study preformed in 2 general practices, 23.5% (40 of 170) of individuals between ages 15 and 30 years had at least 1 SK; prevalence and size increased with age.²

• Approximately half of cases of multiple SKs occur within families, with an autosomal dominant mode of inheritance.³

ETIOLOGY AND PATHOPHYSIOLOGY

• In pigmented SKs, the proliferating keratinocytes secrete melanocyte-stimulating cytokines, triggering activation of neighboring melanocytes.³

• A high frequency of mutations has been found in certain types of SKs in the gene encoding the tyrosine kinase receptor fibroblast growth factor receptor 3 (FGFR3).³ One study found that FGFR3 and transcription factor forkhead box N1 (FOXN1) were highly expressed in SKs but close to undetectable in squamous cell skin cancer.⁴ This may represent a positive regulatory loop between FGFR3 and FOXN1 that underlies a benign versus malignant skin tumor phenotype.

• Reticulated SKs, usually found on sun-exposed skin, may develop from solar lentigines.³

• Multiple eruptive SKs (the sign of Leser-Trélat) have been associated with internal malignancy in case reports (see Figure 164-3),⁵ although this association has been questioned.^6,7

• An eruption of SKs may develop after an inflammatory dermatosis such as severe sunburn or eczema.³

DIAGNOSIS

SKs have a variety of appearances. They are all superficial with an abundance of keratin on the surface causing various patterns.

CLINICAL FEATURES

• Typically oval or round brown plaques with adherent greasy scale (Figure 164-4).

• Color can be black, brown, tan, pink, or a combination of these colors (Figures 164-4, 164-5, 164-6).

• Most often have a velvety to finely verrucous surface and appear to be "stuck on."

• Some are so verrucous they can appear to be warty (Figure 164-6).

• SKs may be large, pigmented, and have irregular borders (Figure 164-5).

• Early SKs may be flat like a solar lentigo (Figure 164-7).

• Many lesions show keratin plugging of the surface (Figures 164-1 and 164-2).

• May have surface ridges of keratin and associated horn cysts (keratin-filled cystic structures). The dermoscopy terms for the horn cysts are comedo-like openings and milia-like cysts (Figure 164-2, see Chapter 111, Dermoscopy). The keratin ridges give many SKs the cerebriform appearance.

• Occasionally, lesions become irritated and can itch, grow, and bleed. These lesions should be considered for biopsy as these features are also suggestive of melanoma.

• Variants of SKs include:

  • Dermatosis papulosa nigra—Consists of multiple brown-black dome-shaped or pedunculated SKs on the face in persons of color (Figures 164-8 and 164-9).

  • Stucco keratosis—Consists of superficial gray-to-light brown flat keratotic lesions usually on the tops of the feet, the ankles, and the back of the hands and forearms (Figure 164-10). They resemble a stucco wall, and that is the origin of the name.

DERMOSCOPIC FEATURES

• Multiple milia-like cysts and comedo-like openings.

• Fissures and ridges of keratin create cerebriform patterns and fat finger-like structures.

• Flatter SKs may have fingerprint-like structures and moth-eaten borders (like solar lentigines).

• Hairpin shaped vessels (other keratinizing tumors such as squamous cell carcinoma may also have hairpin vessels) (see Chapter 111, Dermoscopy).

TYPICAL DISTRIBUTION

• Trunk, face, back, abdomen, extremities; not present on the palms and soles or on mucous membranes. May be present on the areola and breasts (Figures 164-11 and 164-12).

• Dermatosis papulosa nigra is found on the face, especially the upper cheeks and lateral orbital areas (see Figures 164-8 and 164-9).

IMAGING

• No imaging studies are needed even if there is a sudden appearance of multiple seborrheic keratoses as described in the sign of Leser-Trélat (see Figure 164-3). The relationship between malignancy and Leser-Trélat sign is conflicting, and no evidence other than multiple case reports supports the presence of the sign as a predictor of malignancy.^3,7,8 Most likely these are coincidental, and to date there is no scientific mechanism to explain the connection observed by Leser and Trélat. A work-up for malignancy should be based on other signs or symptoms of disease (and age-appropriate screening) and not on the number or rapid appearance of SKs alone.

BIOPSY

• Should be performed if there is a suspicion of melanoma (Figure 164-13). Some melanomas resemble SKs, and a biopsy is needed to avoid missing the diagnosis of melanoma. Do not freeze or curette a suspicious SK; these need a biopsy (usually a shave under the lesion such as a saucerization or deep shave) to send tissue to the pathologist.^9-11 An elliptical excision is not needed in most cases, and a punch biopsy increases the risk of misdiagnosis by incomplete sampling.⁹

DIFFERENTIAL DIAGNOSIS

• Melanoma—When many keratin plugs are visible in the surface of the SK, this helps to distinguish it from a melanoma. However, some melanomas have these same features as part of their morphology. Figure 164-7 is an SK that has the ABCDE features (Asymmetry, Border irregular, Color variation, Diameter >6 mm, Evolving) of melanoma (Chapter 179, Melanoma). A biopsy was performed and the lesion was proven to be benign. In Figure 164-13, a possible SK turned out to be a melanoma in situ. Figure 164-14 is a melanoma on the vulva that had appeared similar to an SK, and it was only because dermoscopy revealed the blue-white veil that a biopsy was done and the melanoma was not missed.

• Solar lentigo—Flat, uniformly medium or dark brown lesion with sharp borders (Chapter 175, Lentigo Maligna). These are flat and seen in sun-exposed areas, typically on the face or back of the hands. Also called liver spots, these hyperpigmented areas are not palpable, whereas an SK is a palpable plaque even when the SK is thin (Figure 164-7). Flat solar lentigines can evolve into seborrheic keratoses. While most SKs do not start as solar lentigines, some SKs do start as a solar lentigo (Figure 164-15).

• Lichen planus–like keratosis (LPLK) is a regressing SK. With regression these lesions will show blue-gray granules and dots on dermoscopy, reflecting melanophage activity. These can be confused with melanomas and should be biopsied to rule out melanoma.

• Wart—Cutaneous neoplasm caused by HPV (Chapter 137, Common Warts). Warts also have a hyperkeratotic surface like an SK. They tend to be papillomatous with thrombosed vessels and disruption of skin lines. As both warts and SKs are benign, cryotherapy is appropriate for both lesions when treatment is desired.

• Pigmented actinic keratosis (AK)—Although most AKs are nonpigmented and don't look like an SK, occasionally a biopsy of an unknown pigmented plaque will be a pigmented AK secondary to sun damage (Chapter 173, Actinic Keratosis and Bowen Disease).

• An inflamed SK may be confused with a malignant melanoma or a squamous cell carcinoma and should be biopsied to determine the diagnosis. Inflamed SKs show more hairpin vessels under dermoscopy (Figure 164-16).

• Even a basal cell carcinoma (BCC) can have features that suggest an SK. If the SK is atypical with BCC-like features, a biopsy is warranted (Chapter 177, Basal Cell Carcinoma).

MANAGEMENT

FIRST LINE

• Cryosurgery with liquid nitrogen, with a 1-mm halo, is a quick and easy treatment. The risks include pigmentary changes, incomplete resolution, and scarring. Hypopigmentation is the most common complication of this treatment, especially in dark-skinned individuals.

• Shave biopsy—If melanoma or another skin cancer is suspected, perform a shave excision or saucerization just deep enough to get under the lesion and send to pathology (see Chapter 113, Biopsy Principles and Techniques).

SECOND LINE

• Removal of a benign-appearing SK by curettage is one option if one is certain of the diagnosis. After local anesthesia with lidocaine and epinephrine, light electrofulguration can make the curettage easier, and sometimes the SK may be rubbed off with a wet gauze pad. A skin curette works well for this procedure. This is second line because it is more work than a shave excision and does not provide as good a tissue sample for histology. As long as one is not freezing the SK and is using a local anesthetic, it is safest to send the tissue for pathology.

• A new highly concentrated hydrogen peroxide solution, A-101, is being studied for topical treatment of SKs of the face.¹²

FOLLOW-UP

• Follow-up as needed. Patients with multiple SKs do not need special monitoring unless there are other risk factors for skin or internal malignancy.

PATIENT EDUCATION

• Reassure patients that SKs are benign lesions that do not become cancer. Rarely, a skin cancer can arise in an SK. Although SKs may grow larger and thicker with time, this is not usually dangerous.

• Unless the SK is suspicious for cancer or inflamed, removal is for cosmetic purposes only and is often not covered by insurance.

• Although SKs may resolve on occasion, spontaneous resolution does not ordinarily occur.

REFERENCES

PATIENT STORY

A 65-year-old man noted a new growth on his face for 1 year (Figure 165-1A). On close examination, the growth was pearly with a few telangiectasias. The donut shape and presence of sebaceous hyperplasia scattered on other areas of the face were reassuring that this is likely a benign sebaceous hyperplasia. To confirm our clinical impression, the lesion was examined with a dermatoscope (Figure 165-1B). Vessels extending toward the center of the lesion from the periphery but not crossing the center (like the shape of a crown) were seen. This along with the yellow color of the sebaceous glands strongly supported the diagnosis. Because the patient wanted the lesion to be removed, a shave biopsy was performed to completely rule out basal cell carcinoma (BCC). The patient was happy with the cosmetic result and relieved that the pathology showed sebaceous hyperplasia.

INTRODUCTION

Sebaceous hyperplasia (SH) is a common, benign condition of sebaceous glands consisting of multiple asymptomatic small yellow papules with a central depression. The sebaceous lobules of SH are greater in number and higher in the dermis than normal sebaceous glands, and only 1 gland appears enlarged.¹ Consequently, the term hyperplasia appears to be a misnomer, and SH is more accurately classified as a hamartoma (disorganized overgrowth of tissue normally found at that site).¹

EPIDEMIOLOGY

• SH occurs in approximately 1% to 26% of the adult population; the latter number is from a population study of hospitalized patients with a mean age of 82 years.¹

• The prevalence of SH is increased in those with immunosuppression by 10-fold to 30-fold¹; for example, 10% to 30% of patients receiving long-term immunosuppression with cyclosporine have SH.^2,3

• SH has also been reported in infants, where they are considered physiologic,⁴ and in young adults who may have a family history of SH.¹

• SH has been reported overlying other skin lesions including neurofibromas, melanocytic nevi, verruca vulgaris, and skin tags.¹

• Rare forms of SH include giant linear (up to 5 cm in diameter) and functional familial (also called premature or diffuse SH); the latter occur typically around puberty as thick plaque-like lesions with pores resembling an orange peel.¹

ETIOLOGY AND PATHOPHYSIOLOGY

• Sebaceous glands, a component of the pilosebaceous unit, are found throughout the skin, everywhere that hair is found. The greatest number is found on the face, chest, back, and upper outer arms.

• The glands are composed of acini attached to a common excretory duct. In some areas, these ducts open directly onto the epithelial surface, including the lips and buccal mucosa (i.e., Fordyce spots), glans penis or clitoris (i.e., Tyson glands), female areolae (i.e., Montgomery glands), and eyelids (i.e., meibomian glands).¹

• Sebaceous glands are highly androgen sensitive, become increasingly active at puberty, and reach their maximum by the third decade of life.

• The cells that form the sebaceous gland, sebocytes, accumulate lipid material as they migrate from the basal layer of the gland to the central duct, where they release the lipid content as sebum. In younger individuals, turnover of sebocytes occurs approximately every month.

• With aging, the turnover of sebocytes slows; this results in crowding of primitive sebocytes within the sebaceous gland, causing a benign hamartomatous enlargement called SH.¹

• Genetic factors include overexpression of the aging-associated gene Smad7 and parathormone-related protein.⁵ In a small case series, activating HRAS, KRAS, and EGFR mutations were found in 60% of 43 sebaceous gland hyperplasia lesions.⁶

• There is no known potential for malignant transformation, but SH may be associated with nonmelanoma skin cancer in patients following organ transplantation.

RISK FACTORS

• Associated with Muir-Torre syndrome (concurrent or sequential development of a sebaceous neoplasm and an internal malignancy or multiple keratoacanthomas, an internal malignancy, and a family history of Muir-Torre syndrome).

• Immunosuppression.

• Ultraviolet radiation.

DIAGNOSIS

CLINICAL FEATURES

• Lesions appear as yellowish, soft, small papules ranging in size from 2 to 9 mm (Figures 165-1, 165-2, 165-3).¹

• Surface varies from smooth to slightly verrucous.

• Lesions can be single or multiple.

• Increasing number of lesions with aging; higher frequencies after 40 to 50 years of age.¹

• In functional familial SH, lesions may appear thick and plaque-like, with pores that resemble an orange peel; the skin in these patients is quite oily.¹

• Lesions may become red and irritated and bleed after scratching, shaving, or other trauma; they may be associated with telangiectasias.

• Central umbilication (donut shape) from which a small amount of sebum can sometimes be expressed (Figures 165-1, 165-2, 165-3).

TYPICAL DISTRIBUTION

• Most commonly located on the face, particularly the nose, cheeks, and forehead. May also be found on the chest, areola, mouth, and, rarely, the vulva.^1,7

IMAGING

• Dermoscopy can aid in distinguishing between nodular BCC and SH; a vascular pattern with orderly winding, scarcely branching vessels extending toward the center of the lesion is specific for SH. These are described as crown vessels that extend through the yellow sebaceous glands (see Figure 165-1B).⁸

BIOPSY

• Not usually necessary unless concerned about BCC.

DIFFERENTIAL DIAGNOSIS

• Nodular BCC—These lesions can appear as waxy papules with a central depression that may ulcerate, most commonly located on the head, neck, and upper back. They may have a pearly appearance, surface telangiectases, and bleed easily (Figures 165-4 and 165-5).

• Fibrous papule of the face is a benign, firm, papule of 1 to 5 mm that is usually dome-shaped and indurated with a shiny, skin-colored appearance. Most lesions are located on the nose and, less commonly, on the cheeks, chin, neck, and, rarely, the lip or forehead.

• Milia are common, benign, keratin-filled cysts (histologically identical to epidermoid cysts) that occur in persons of all ages. They are 1 to 2 mm, superficial, uniform, pearly white to yellowish, domed lesions usually occurring on the face (Figure 165-6).

• Molluscum contagiosum are firm, smooth, usually 2- to 6-mm umbilicated papules that may be present in groups or widely disseminated on the skin and mucosal surfaces. The lesions can be flesh colored, white, translucent, or even yellow in color. Lesions generally are self-limited but can persist for several years (Chapter 136, Molluscum Contagiosum).

• Syringoma is a benign adnexal neoplasm formed by well-differentiated ductal elements. They are 1- to 3-mm skin-colored or yellowish dermal papules with a rounded or flat top arranged in clusters, and symmetrically distributed primarily on the upper parts of the cheeks and lower eyelids (see Figure 165-6).

• Xanthomas are deposits of lipid in the skin or subcutaneous tissue that manifest clinically as yellowish papules, nodules, or tumors. They are usually a consequence of primary or secondary hyperlipidemia and occur in patients older than age 50 years. The lesions are soft, velvety, yellow, flat, polygonal papules that are asymptomatic and usually bilateral and symmetric (Chapter 232, Hyperlipidemia and Xanthomas).

MANAGEMENT

SH does not require treatment but can be removed for cosmetic purposes or if it becomes irritated. Evidence supporting treatment comes primarily from case series.

• Options for removal include cryotherapy, electrodesiccation, topical chemical treatments (e.g., with bichloracetic acid or trichloroacetic acid), oral isotretinoin (10 to 40 mg a day for 2 to 6 weeks), laser treatment (e.g., with argon, carbon dioxide, or pulsed-dye laser), photodynamic therapy (PDT; i.e., combined use of 5-aminolevulinic acid and visible light),⁹ shave excision, and punch excision.¹ Complications of these therapies include atrophic scarring and changes in pigmentation.

FIRST LINE

• The easiest and most effective method in the family physician's office is to lightly electrodesiccate the SH with electrosurgery using 2 to 2.3 watts with a blunt-tip electrode. This can be done without anesthesia and provides a good cosmetic result. The electrode is moved in a circular or linear fashion around or across the SH until the tissue turns gray (Figure 165-7).

• If there is any suspicion that what appears to be sebaceous hyperplasia may be a BCC, perform a shave biopsy as treatment and send the tissue for histology.

SECOND LINE

• In one case series of 20 patients with sebaceous hyperplasia, use of isotretinoin at 1 mg/kg/day significantly decreased the number of lesions from an average of 24 lesions per patient to 2 per patient at 2 months and 4 per patient at 2 years.¹⁰ Discontinuation is associated with high relapse rates.¹¹

• Authors of a systematic review of laser treatment and PDT for sebaceous hyperplasia found that use of wavelength-specific laser of 1720 nm had better outcomes with minimal damage.¹¹ In addition, pretreatment with carbon dioxide laser ablation or pulsed-dye laser before PDT offered higher cure rates over stand-alone laser or PDT treatments using fewer sessions with similar transient side effects.

FOLLOW-UP

No follow-up is needed.

REFERENCES

PATIENT STORY

A 25-year-old woman reports a firm nodule on her leg that gets in the way of shaving her leg (Figure 166-1). Upon questioning, the nodule may have appeared in that location after she cut her leg shaving 1 year ago. She is worried it could be a cancer and wants it removed. Close observation showed a brown halo and a firm nodule that dimpled down when pinched. A diagnosis of a dermatofibroma (DF) was made and the choices for treatment were discussed.

INTRODUCTION

DF is a benign fibrohistiocytic tumor, usually found in the mid dermis, composed of a mixture of fibroblastic and histiocytic cells. These scarlike nodules are most commonly found on the legs and arms of adults.

SYNONYMS

Also called benign fibrous histiocytoma.

EPIDEMIOLOGY

• Occurs more often in women (male-to-female ratio is 1:2).¹

• Found in patients of all races.

• Approximately 20% occur in patients younger than age 20 years.¹ In one case series, 80% occurred in people between the ages of 20 and 49 years.²

ETIOLOGY AND PATHOPHYSIOLOGY

• Uncertain etiology—Nodule may represent a fibrous reaction triggered by trauma, a viral infection, or insect bite; however, DFs show clonal proliferative growth seen in both neoplastic and inflammatory conditions.³

• The epidermal regions of DFs are similar to seborrheic keratosis in terms of histologic features and activation of fibroblast growth factor receptor 3 and forkhead box N1.⁴

• Multiple DFs (i.e., >15 lesions) have been reported associated with systemic lupus erythematosus, HIV infection, Down syndrome, Graves disease, or leukemia and may represent a worsening of immune function.¹ A case of familial eruptive DFs has also been reported associated with atopic dermatitis.⁵

DIAGNOSIS

CLINICAL FEATURES

• Firm to hard nodule; skin is freely movable over the nodule, except for the area of dimpling.

• Color of the overlying skin ranges from flesh to gray, pink, red, blue, brown, or black (Figures 166-2 and 166-3), or a combination of hues (Figure 166-4).

• Dimples downward when compressed laterally because of tethering of the overlying epidermis to the underlying nodule (see Figure 166-3).

• Usually asymptomatic but may be tender or pruritic.

• Size ranges from 0.3 to 10 mm; usually less than 6 mm. Rarely, DFs grow to larger than 5 cm.⁶

• May have a hyperpigmented halo and a scaling surface (see Figure 166-4).

• DFs can rarely be located entirely within subcutaneous tissue.⁷

DERMOSCOPY

• Dermoscopy is a useful diagnostic technique for DF (Figure 166-5). Although the most common finding is a peripheral pigment network with a central white area (34.7% of cases), 10 dermoscopic patterns have been identified; in a large case series, pigment network was observed in 71.8% (3% atypical pigment network).⁸ (See Chapter 111, Dermoscopy.) Another common pattern contains ringlike globules in the central scar like area (Figure 166-6).

TYPICAL DISTRIBUTION

• May be found anywhere, but usually on the legs and arms, especially the lower legs. In one case series, 70% were on the lower extremities.²

BIOPSY

• A punch biopsy can be both diagnostic and therapeutic. DFs have been reported with overlying basal cell carcinoma and associated melanoma^9,10; rarely, DFs are malignant.¹¹

• Histologically, DFs are classified as fibrous histiocytomas (80%) followed by aneurysmal (5.7%), hemosiderotic (5.7%), epithelioid (2.6%), cellular (2.1%), lipidized (2.1%), atrophic (1.0%), and clear cell (0.5%) variants.¹² It is recommended to fully excise cellular DFs with clear margins, as these tend to be more aggressive and may be malignant.^11,13

DIFFERENTIAL DIAGNOSIS

DFs can be confused with the following malignant tumors; diagnosis based on histology and excision should be undertaken for enlarging or ulcerating tumors:

• Dermatofibrosarcoma protuberans—A malignant fibrotic tumor of the skin and subcutaneous tissues (Figure 166-7). A punch biopsy may provide adequate tissue to make the diagnosis, but a larger incisional biopsy may be needed. These are dangerous tumors with a high risk of recurrence, so they should be referred to Mohs surgery for complete excision. They resemble a large irregular DF, but a DF is not a precursor to this. It is a separate malignant tumor, not the result of a DF growing out of control.

• Pseudosarcomatous DF—A rare connective tissue tumor arising on the trunk and limbs in young adults.

• Malignant fibrous histiocytoma—A common soft-tissue sarcoma occurring in the extremities. Presentation as a primary cutaneous lesion is rare; more often presents as a metastasis from another location such as the breast.

Many benign lesions have a similar appearance, including:

• Pigmented seborrheic keratosis—May be macular and often larger than DF. Distinguished by surface cracks, verrucous features, stuck-on appearance, and adherent greasy scale (Chapter 164, Seborrheic Keratosis).

• Hypertrophic scar—Occurs within previous wounds or lacerations.

• Neurofibroma—Benign Schwann cell tumors; single lesions are seen in normal individuals. Cutaneous tumors tend to form multiple, soft, pedunculated masses, whereas subcutaneous nodules are skin-colored soft nodules attached to peripheral nerves. The latter show invagination similar to that in DF (Chapter 245, Neurofibromatosis).

MANAGEMENT

FIRST LINE

• No treatment is necessary unless the diagnosis is questioned or symptoms warrant.

• Punch excision or shave excision may be used for small lesions; with the latter technique, the healed area may remain hard as a result of remaining fibrous tissue.

• Larger lesions may require an elliptical (fusiform) excision, down to the subcutaneous fat.

• One author noted that DFs occurring on the face often have involvement of deeper structures and an increased rate of local recurrences, and therefore recommended excision with wider margins in comparison with DFs occurring on the extremities.¹⁴

SECOND LINE

• Cryotherapy has also been used, but the cure rate is lower and lesions may recur.

• Several case reports found success in treating multiple DFs with carbon dioxide laser.¹⁵

PROGNOSIS

• Although DFs are usually unchanging and persist indefinitely, there are reports of spontaneous regression.¹⁶

• Following excision, DFs have a low recurrence rate of less than 2%, with higher recurrence believed to occur in cellular, aneurysmal, and atypical types.^8,13

• A higher rate of recurrence has been noted in the subcutaneous and deep types, and in lesions located on the face, in which a recurrence rate of 15% to 19% has been reported.^17,18

• In a report of 7 cases of clinically aggressive DFs arising in various locations, mean size of the lesions was 3 cm (range 1–9 cm) and infiltration of the subcutis was seen in 5 of 7 cases.¹¹ Local recurrences were seen in 6 cases and metastases in 6 cases (identified between 3 months and 8 years after diagnosis); 2 patients died of the disease. Histology of the primary tumor was more often the cellular type (4 of 7 cases). Five neoplasms showed chromosomal aberrations by array-comparative genomic hybridization, which may be helpful in identifying cases with metastatic potential.

PATIENT EDUCATION

• DFs are best left alone if they are relatively asymptomatic and stable.

REFERENCES

PATIENT STORY

A 22-year-old woman comes in to the clinic for a new growth that has evolved over the past 3 months on her finger (Figure 167-1). It started at the end of her pregnancy and she is now postpartum. The growth is painless, but bleeds easily. She was diagnosed with a probable pyogenic granuloma (PG) and treatment options were discussed. She opted for shave excision, followed by curettage and electrodesiccation (Figure 167-2). The tissue was sent for pathology and confirmed the diagnosis of PG. On follow-up the site was healing well and the patient was very happy with the result.

INTRODUCTION

Pyogenic granuloma (PG) is a relatively common benign acquired vascular growth of the skin and mucous membranes.

SYNONYMS

PG is also known as lobular capillary hemangioma (LCH) due to its histologic appearance. PG is a misnomer as it is neither pyogenic nor granulomatous. However, it often has a purulent-appearing exudate that explains how it got its name (Figure 167-3).

EPIDEMIOLOGY

• Seen most commonly in children, teens, and young adults. Mean onset in children is age 6.7, but can occur throughout childhood. Generally acquired, but 1% are present at birth.¹

• Oral lesions are more common in women, particularly in the 2nd and 3rd decades of life, and in pregnancy.¹

• PGs have also rarely been reported in the GI tract, nose, conjunctiva, and subcutaneous and intravenous locations.

ETIOLOGY AND PATHOPHYSIOLOGY

• Etiology is unknown. PGs may be associated with prior trauma (see Figure 167-3), wound, and hormonal changes, but a direct relationship has not been proven.

• It is hypothesized that pro-angiogenic growth factors play a role in development of PG. This may account for the reported response of pediatric PGs to beta blockers.²

• Histopathology demonstrates proliferation of capillaries and venules with neutrophilic infiltrates, in a lobular pattern.^3,4

RISK FACTORS

• Prior local trauma (in a minority of patients).¹

• Pregnancy (Figure 167-4) and oral contraceptives may be risk factors, possibly due to the effect of hormones on angiogenesis.

• Medications (including retinoids, protease inhibitors, and antineoplastic agents).³

• Bartonella—associated with increased Bartonella seropositivity in one report.¹

• Manipulation—infrequently, satellite PG lesions can occur.

DIAGNOSIS

CLINICAL FEATURES

• Painless red papule or nodule that is friable and bleeds easily even with minor trauma. Several millimeters to several centimeters in size.

• Usually singular, but occasionally multiple lesions.

• Develops rapidly over several weeks.

• May ulcerate (Figure 167-5) or crust over.

TYPICAL DISTRIBUTION

• Most commonly found on the head, neck, trunk, and upper limbs. Hands and fingers are the most frequent sites on the upper limb (Figure 167-6). PGs are also found on the scalp (see Figure 167-5).

• In pregnant women, PG found most frequently on the oral mucosa.

• Rarely, lesions may be subcutaneous, IV, or visceral.

DERMOSCOPY

• Dermoscopy reveals reddish homogenous areas, white collarettes, "white rail" lines and ulceration, all of which are associated with PGs (Figure 167-7).⁵

• Multiple patterns or combinations of the above can be seen in PGs.⁵

• Reddish homogeneous area, white collarettes, and white rail lines together had a specificity for PG of 100%.⁵

BIOPSY

• Capillaries in edematous stroma with associated neutrophilic infiltrate. Over time, develops an increasingly lobular pattern. Often the lesion has a surrounding epidermal collarette. Develops increasing fibrosis before regressing.^1,3,4,6

• It is crucial to send the specimen to pathology to rule out amelanotic melanoma (Figure 167-8).

DIFFERENTIAL DIAGNOSIS

• Malignancies that can be mistaken for PG include basal cell cancer, squamous cell cancer, keratoacanthoma, amelanotic melanoma (see Figure 167-8), cutaneous metastatic lesions, and Kaposi sarcoma. Therefore, every PG that is excised should be sent to pathology.

• Benign tumors that can resemble PG include hemangiomas (Figure 167-9), angiokeratomas, and fibrous papules.

• Bacillary angiomatosis may be confused with PG, and its histopathology has similar features (see Figure 226-10). It is a rare infection seen more commonly in patients in patients with AIDS or advanced immunosuppression.⁴

MANAGEMENT

PGs eventually resolve slowly over time. However, patients often opt for treatment for cosmetic reasons or due to bleeding. Treatment options include both pharmacologic and surgical approaches. If clinicians have any diagnostic uncertainty, the lesion should be removed and sent to pathology.

Treatment choice is usually driven by the patient's age, location of the lesion, cosmetic concerns, and whether there is any diagnostic uncertainty. Younger pediatric patients with typical PG lesions may be treated with topical agents or cryotherapy.

OBSERVATION

• Untreated PGs become increasingly fibrotic and eventually resolve over months to years. Most patients want treatment because of the frequent bleeding.

PHARMACOLOGIC

• A number of small series of patients have been treated successfully with topical imiquimod 5% cream. The frequency of application has varied from three times a week to twice daily for periods ranging from 2 to 8 weeks.⁷ SORⒸ

• Topical timolol 0.5% gel is frequently used for treatment of superficial infantile hemangiomas. Recently, case reports indicate that PG may be treated successfully with topical timolol two to three times a day for weeks or months.² SORⒸ

PROCEDURES

• Surgical excision has the lowest recurrence rate (3.7%), but has a higher incidence of scarring (55%).⁸ SORⒸ It is not uncommon for PGs of the lip to recur unless treated with surgical excision (Figure 167-10).

• Shave excision followed by curetting and electrodesiccation of the base has a recurrence rate of 10%, with scarring in approximately 30%.⁸ SOR PGs bleed extensively when manipulated or cut. It is important to use lidocaine with epinephrine, wait 10 minutes for the epinephrine to work, and have an electrosurgery device to control bleeding. Cut the PG off with a blade and send to pathology. Curetting the base will also help stop the bleeding and prevent recurrence. The base is curetted and electrodesiccated until the bleeding stops. SORⒸ

• Laser surgery often requires more than one treatment session, and scarring and recurrence rates are variable.⁸ SORⒸ

• Cryotherapy has low recurrence rates but often requires more than one treatment, and it is often associated with scarring (42%) (Figure 167-11).^8,9 SORⒸ

PROGNOSIS

• PGs usually develop over several weeks. They are generally present for months and sometimes years. Over time, they become increasingly fibrotic and involute.¹

FOLLOW-UP

• In 2 to 3 weeks to check on resolution of the lesion, wound healing, and pathology findings.

PATIENT EDUCATION

• Inform patients that these lesions are benign and will often resolve spontaneously over months to years. However, there are several effective treatment options available if desired for cosmetic reasons or to prevent bleeding.

• If the lesion recurs, early follow-up is appropriate, as small lesions are generally easier to treat than large ones.

REFERENCES