Enlarging brown spots - Clinical Advisor

Enlarging brown spots

Slideshow

  • Case #1

    September 2015 Dermatology Look-Alikes

    Case #1

  • Case #2

    September 2015 Dermatology Look-Alikes

    Case #2

Case #1

A woman, aged 65 years, presents for evaluation of a “mole” or spot that has been present on her arm for a few years. She says that the spot that worried her was slightly bigger than the rest of the “brown spots” on her body, it had increased slightly in size, and it was bothersome to her. She denies any pain, bleeding, or pruritus. She reports that she has spent many years tanning in the sun and that her mother has several “age spots.”

Case #2

A man, aged 57 years, presents for the evaluation of several brown spots that have developed on his back over the last few years. He is worried about some of the bigger spots growing in size. He denies any pain, bleeding, or pruritus. He admits to many years of sun exposure in the past. He also admits to several sunburns when he was younger. He is currently using sunscreen occasionally.


This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read White papules and 
follicular abnormalities on a toddler’s face and Red-brown papules and plaques on the head and body. Then take the post-test here.


Case #1Seborrheic keratosis (SK) is a benign epidermal tumor that is most commonly found in middle-aged and older adults. Also known as senile wart, senile keratosis, basal cell papilloma, verruca senilis, and seborrheic wart, SK typically presents as a well-circumscribed...

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Case #1

Seborrheic keratosis (SK) is a benign epidermal tumor that is most commonly found in middle-aged and older adults. Also known as senile wart, senile keratosis, basal cell papilloma, verruca senilis, and seborrheic wart, SK typically presents as a well-circumscribed lesion that is brown, black, or light tan in color. 


SK may appear as a single growth or a cluster of growths. Most lesions are 0.5 cm to 1.5 cm in diameter, but tiny papules measuring 0.2 mm to 0.3 mm in diameter and large plaques measuring several centimeters in diameter can occur.1 The lesions of SK may be round, oval, or irregular in shape. In its initial stages, SKs usually have a velvety or finely verrucous surface, but over time, they enlarge, thicken, and develop a verrucous, rough, warty surface. The lesions may be flat or elevated, and they are often said to have a “stuck-on” or “pasted-on” appearance. They can appear anywhere except for the palmoplantar areas and mucous membranes, but they most often present on the trunk.2

SKs are the most common benign growth on adult skin, and its prevalence rises with increasing age. They are traditionally said to appear in or after the fifth decade of life. However, cases of SK in young individuals have also been reported.2,3

The size of SKs also tends to increase with increasing age, with young individuals having a higher proportion of lesions that measure less than 3 mm in diameter and older individuals having a higher proportion of lesions that are greater than 3 mm in diameter.2 There is no difference in prevalence between males and females. 


The underlying pathogenesis of SK is not fully understood, but heredity, aging, chronic sun exposure, and human papilloma virus have been proposed as risk factors.4 Somatic mutations of fibroblast growth factor receptor 3 (FGFR3) likely have a causative role in the pathogenesis of SKs. FGFR3 mutations have been detected in 39% to 85% of human SKs, and inducing FGFR3 mutations in the epidermis has been shown to trigger the development of SK lesions.5 Since FGFR3 mutations are not found to be present in all SKs, it is likely that SK is polygenic and multifactorial. 


Histologically, SKs are characterized by a proliferation of small basaloid keratinocytes.1 The exact histopathologic appearance of SK differs according to the subtype(s) of the lesion, but all have the common characteristics of hyperkeratosis, acanthosis, and papillomatosis to some degree. 


The histologic subtypes of SK include the hyperkeratotic type, acanthotic type, clonal type, reticulated type, irritated type, and pigmented type.4 These subtypes exhibit considerable variety, and multiple types may be observed in the same lesion. The hyperkeratotic type displays pronounced papillomatosis and mild acanthosis; it has a verruciform silhouette and thickened keratin layer.1,6 The acanthotic type shows slight papillomatosis and hyperkeratosis, greatly thickened epidermis, basaloid cell proliferation, and horn cysts.1,6 The clonal type is characterized by a proliferation of sharply demarcated intraepithelial nests of basaloid cells, and the reticulated type is characterized by numerous, thin, double rows of basaloid epidermal cells that extend from the epidermis and demonstrate branching and interweaving in the dermis.7 The irritated type shows a proliferation of larger keratinocytes resembling spinal layer cells, horn pearl formation, and a lichenoid inflammatory infiltrate in the dermis.1,7

Pigmentation can be seen with any subtype of SK but is most often seen within the acanthotic and reticulated subtype.7 Melanin pigment is most often present within basal keratinocytes.7

Sudden eruptions of multiple SKs or a rapid increase in the number and/or size of existing SKs are signs of Leser-Trélat syndrome and may signal an underlying malignant disease, most commonly adenocarcinomas of the colon, breast, or stomach. Therefore, clinicians should consider screening patients with symptoms of Leser-Trélat for internal malignancies.8

Diseases that mimic SK include epidermal nevus, actinic keratosis, verruca vulgaris, acanthosis nigricans, basal cell carcinoma, solar lentigo, and melanoma.4

Most SKs are diagnosed clinically by their appearance, but dermoscopy can aid in the diagnosis of SK. Dermoscopic features of SK include a moth-eaten border, milia-like cysts, comedo-like openings, fissures, ridges, hyperkeratosis, grid-like networks of pigmented lines, and hairpin-shaped blood vessels.9

Early SKs share many histologic and clinical features with solar lentigo and may evolve from solar lentigo. Solar lentigo typically occurs on the face, arms, and hands, and appears less often on the trunk than SK. Unlike most mature SK, solar lentigo does not have a “stuck-on” appearance or rough surface.


SKs may resemble melanomas, as both can be irregular in shape and appear with variable dark colors. However, SKs tend to vary less in color and have a rougher surface. If the diagnosis is in question, a biopsy may be indicated.


SKs are usually asymptomatic and do not require treatment, but some SKs may be bothersome because of aesthetic concerns, pruritus, or inflammation due to chafing from clothing. Spontaneous regression of SKs is not expected but does occur rarely. Topical steroids can provide symptomatic relief for irritated SKs.


Removal of SKs can be achieved by several means. Cryotherapy with liquid nitrogen is commonly used to remove SKs, but this method is less effective at removing large, thick lesions. Curettage with or without electrocautery and electrocautery alone are common treatments. Laser treatment with a carbon dioxide laser or erbium:yttrium-aluminum-garnet (Er:YAG) system is also a therapeutic option.1 Lesions do not usually recur after therapy. 


In our case, a biopsy was performed on the patient’s lesion, which confirmed the diagnosis. The patient was interested in removal of the lesion. After reassurance and education regarding sun protection, the lesion was treated with liquid nitrogen therapy, with resolution in one week.


Case #2

Solar lentigines (SLs; singular: solar lentigo) are caused by hyperplasia of keratinocytes and melanocytes, with increased accumulation of melanin in the keratinocytes.10 SLs have a variety of names that reflect the link between SL and aging and sun exposure: age spots, senile freckles, lentigo senilis, liver spots, sun-induced freckles, and sunburn freckles. 


SLs increase in prevalence with age and affect more than 90% of Caucasians aged more than 50 years.11 The lesions are induced by ultraviolet light exposure and therefore occur predominantly on sun-exposed skin, particularly the face, arms, hands, shoulders, and upper back.1 Chronic and acute sun exposure, even before age 20 years, is a strong risk factor for the development of SL.12,13 Psoralen ultraviolet A (PUVA)-induced lentigines can develop as the result of PUVA therapy. 


The lesions of SL usually have a uniform light brown color but can vary from dark brown to black.10 SLs vary in size from a few millimeters to a few centimeters in diameter and may be oval, round, or irregular in shape with or without a well-demarcated border.10,14 One variant of SL, “ink-spot” lentigo, has a jet-black color and an irregular outline, with wire-like or beaded projections.15

R160W, a variant of melanocortin receptor 1 (MC1R), a G-protein-coupled receptor on melanocytes, has been associated with a higher risk of SL. R160W shows aberrant anterograde trafficking and intracellular retention, accounting for its reduced impaired cell surface expression and weakened receptor function.16 It has been proposed that decreased sensitivity to MC1R as a result of the variant protein may alter melanosome transfer and therefore be an important factor in the development of SL. 


SL is usually diagnosed by its clinical appearance, but a dermatoscope can aid in its diagnosis. Dermoscopic features of SL include a moth-eaten border, homogenous light brown pigmentation (“jelly sign”), pigment network, fingerprint-like areas, pseudo-network pattern, and symmetric follicular pigmentation.10

SLs are characterized histologically by elongated, club-shaped rete ridges with small nub-like extensions (“dirty feet”), hyperpigmentation in the basal keratinocytes due to abnormal melanin retention, and commonly, an increase in the number of melanocytes.10 Varying degrees of solar elastosis are usually present in the dermis.18

The differential diagnosis of SL includes freckles, lentigo maligna, early seborrheic keratosis (SK), pigmented actinic keratosis, and lichen-planus-like keratosis, as all of these can share dermoscopic and histopathologic characteristics as well as the clinical appearance of a flat, pigmented macule of varying size and shape.19

Unlike freckles, which fade in the absence of sun exposure, SLs are stable in color regardless of sun exposure. Furthermore, in contrast to freckles, SLs contain an increased number of melanocytes, and SLs often grow larger than freckles by up to several centimeters in diameter. 


Macules of lentigo maligna tend to develop as solitary lesions, are darker in color, and are more irregularly pigmented than those of SL. Unlike SL, lentigo maligna demonstrates asymmetrical pigmented follicular openings, rhomboidal structures, annular-granular structures, and gray pseudo-network on dermoscopy.20 Biopsy is indicated for suspicious lesions, as lentigo maligna can progress to lentigo maligna melanoma. 


Initial SKs resemble SLs, and a SL may evolve to form 
a pigmented SK. Developed SKs can be distinguished from SL by SK’s “stuck-on” appearance and uneven, warty surface. 


Dermoscopy can help distinguish SL from pigmented actinic keratosis and lichen-planus-like keratosis. Dermoscopic criteria for pigmented actinic keratosis include slate-gray dots and areas, annular-granular pattern, rhomboidal structures, black globules and digs, broken pseudo-network, and keratin plugs.19 Dermoscopic criteria of lichen-planus-like keratosis include brownish-gray, bluish-gray, or whitish-gray granules that may be localized or diffuse.19 Unlike flat seborrheic dermatoses and pigmented actinic keratoses, SLs do not demonstrate epidermal hyperkeratosis. 


SLs are benign lesions that do not require treatment, but patients should be advised to use sunscreen as a preventative measure. Some patients, however, may find SLs aesthetically bothersome and desire treatment. 


Many treatment options exist to remove them. Cryotherapy with liquid nitrogen is one of the most widely used and effective techniques to remove SLs. Trichloroacetic acid, usually at 35% concentration, can be applied with or without abrasion. Retinoic acid and topical bleaching agents, such as hydroquinone, have been shown to reduce the pigment of SLs. Recently, lasers have been used with increasing frequency to treat SLs. Because melanin absorbs a broad spectrum of light from 351 nm to 1,064 nm, many types of lasers are effective. Some of the most commonly used lasers include the pulsed dye (510 nm), frequency-doubled Neodymium:yttrium-aluminum-garnet (Nd:YAG; 532 nm), Q-switched ruby (694 nm), and Q-switched Nd:YAG (1,064 nm).21

The patient in our case was reassured and educated about his diagnosis of SL. Daily sun protection was recommended. Liquid nitrogen therapy was offered, but the patient declined, electing instead for observation and sun protection.

Kate Travis, BA, is a medical student and Rana Mays, MD, is a dermatology resident at Baylor College of Medicine in Houston.


This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read White papules and 
follicular abnormalities on a toddler’s face and Red-brown papules and plaques on the head and body. Then take the post-test here.


References


  1. Baykal C, Yazganoglu KD. Clinical Atlas of Skin Tumors. Berlin: Springer-Verlag Berlin Heidelberg; 2014:3-37. 

  2. Gill D, Dorevitch A, Marks R. The prevalence of 
seborrheic keratoses in people aged 15 to 30 years: Is the term senile keratosis redundant? Arch Dermatol. 2000;136(6):759-762. Available at archderm.jamanetwork.com/article.aspx?articleid=190329 

  3. Memon AA, Tomenson JA, Bothwell J, Friedmann 
PS. Prevalence of solar damage and actinic keratosis in a Merseyside population. Br J Dermatol. 2000;142(6):
1154-1159. 

  4. Phulari RG, Buddhdev K, Rathore R, Patel S. Seborrheic keratosis. J Oral Maxillofac Pathol. 2014;18(2):327-330. Available at ncbi.nlm.nih.gov/pmc/articles/PMC4196312 

  5. Hafner C, Hartmann A, van Oers JM, et al. FGFR3 
mutations in seborrheic keratoses are already present in flat lesions and associated with age and localization. Mod Pathol. 2007;20(8):895-903. Available at nature.com/modpathol/journal/v20/n8/full/3800837a.html 

  6. Elder DE, ed. Lever’s Histopathology of the Skin. 
10th ed. Philadelphia, Pa.: Lippincott Williams & Wilkins; 2009:795-798. 

  7. Busam KJ. Dermatopathology. 1st ed. Philadelphia, Pa.: Saunders Elsevier; 2010:336-343. 

  8. Ponti G, Luppi G, Losi L, et al. Leser-Trélat syndrome in patients affected by six multiple metachronous primitive cancers. J Hematol Oncol. 2010;3:2. Available at jhoonline.org/content/3/1/2 

  9. Braun RP, Rabinovitz HS, Krischer J, et al. Dermoscopy of pigmented seborrheic keratosis: A morphological study. Arch Dermatol. 2002;138(12):1556-1560. Available at 
archderm.jamanetwork.com/article.aspx?articleid=479104 

  10. Wang SQ, Rabinovitz HS, Oliveiro MC, Marghoob AA. Solar 
lentigines, seborrheic keratoses, and lichen planus-like keratosis. In: Marghoob AA, Malvehy J, Braun RP, eds. Atlas of Dermoscopy. 2nd ed. London: Informa Healthcare; 2012:58-69.

  11. Ortonne JP. Pigmentary changes of the aging skin. Br J Dermatol. 1990;122(Suppl 3):21-28. 

  12. Reguiaï Z, Jovenin N, Bernard P, Derancourt C. Melanoma, past severe sunburns and multiple solar lentigines of the upper back and shoulders. Dermatology. 2008;216(4):330-336. 

  13. Bastiaens M, Hoefnagel J, Westendorp R, et al. Solar lentigines are strongly related to sun exposure in contrast to ephelides. Pigment Cell Res. 2004;17(3):225-229. 

  14. Clarke LE, Clarke JT, Helm KF. Color Atlas of Differential Diagnosis in Dermatopathology. 1st ed. New Delhi, India: Jaypee Brothers Medical Publishers Ltd; 2014. 

  15. Bolognia JL. Reticulated black solar lentigo (‘ink spot’ lentigo). 
Arch Dermatol. 1992;128(7):934-940. 

  16. Sánchez-Laorden BL, Herraiz C, Valencia JC, et al. Aberrant trafficking of human melanocortin 1 receptor variants associated with red hair and skin cancer: Steady-state retention of mutant forms in the proximal golgi. J Cell Physiol. 2009;220(3):640-654. Available at ncbi.nlm.nih.gov/pmc/articles/PMC2705480 

  17. Ezzedine K, Mauger E, Latreille J, et al. Freckles and solar lentigines have different risk factors in Caucasian women. J Eur Acad Dermatol Venereol. 2013;27(3):e345-e356. 

  18. Barnhill RL, Piepkorn MW, Busam KJ, eds. Pathology of Melanocytic Nevi and Melanoma. 3rd ed. Berlin: Springer-Verlag Berlin Heidelberg; 2014:65-68. 

  19. Lallas A, Argenziano G, Moscarella E, et al. Diagnosis and management of facial pigmented macules. Clin Dermatol. 2014;32(1):94-100. 

  20. Tanaka M, Sawada M, Kobayashi K. Key points in dermoscopic differentiation between lentigo maligna and solar lentigo. J Dermatol. 2011;38(1):53-58. 

  21. Ortonne JP, Pandya AG, Lui H, Hexsel D. Treatment of solar lentigines. J Am Acad Dermatol. 2006;54(5 Suppl 2):S262-S271. 


All electronic documents accessed on September 8, 2015.



This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read White papules and 
follicular abnormalities on a toddler’s face and Red-brown papules and plaques on the head and body. Then take the post-test here.


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