Seborrheic keratoses (SKs) are very common benign epithelial skin tumors encountered in the adult population. Seborrheic Keratosis is a skin condition in which there is brown to black color skin gowth which is slightly raised. It originates in the epidermis, and a proliferation of immature keratinocytes is present.

 

Seborrhoeic keratosis (or seborrheic keratosis) is also called basal cell papilloma, senile wart, brown wart, wisdom wart, or barnacle.  The descriptive term, benign keratosis, is a broader term that is used to include the following related scaly skin lesions:

  • Seborrhoeic keratosis 
  • Solar lentigo
  • Lichen planus-like keratosis (which arises from a seborrhoeic keratosis or a solar lentigo).
 

Seborrheic keratoses are harmless and not contagious. They don't need treatment, but you may decide to have them removed if they become irritated by clothing or you don't like how they look.

 

The name is misleading, because they are not limited to a seborrhoeic distribution (scalp, mid-face, chest, upper back) as in seborrhoeic dermatitis, nor are they formed from sebaceous glands, as is the case with sebaceous hyperplasia, nor are they associated with sebum — which is greasy.

 

The precise cause of seborrhoeic keratoses is not known.

Seborrhoeic keratoses are considered degenerative in nature. As time goes by, seborrhoeic keratoses become more numerous. Some people inherit a tendency to develop a very large number of them. The various observations seen in seborrheic keratosis are:

  • Eruptive seborrhoeic keratoses can follow sunburn or dermatitis.
  • Skin friction may be the reason they appear in body folds.
  • Viral cause (eg human papillomavirus)
  • Stable and clonal mutations or activation of FRFR3, PIK3CA, RAS, AKT1 and EGFR genes are found in seborrhoeic keratoses.
  • Seborrhoeic keratosis can arise from solar lentigo.
  • FRFR3 mutations also arise in solar lentigines. These mutations are associated with increased age and location on the head and neck, suggesting a role of ultraviolet radiation in these lesions.
  • Seborrhoeic keratoses do not harbour tumour suppressor gene mutations.
  • Epidermal growth factor receptor inhibitors (used to treat cancer) often result in an increase in verrucal (warty) keratoses.

Variants of seborrhoeic keratoses

Variants of seborrhoeic keratoses include:

  • Solar lentigo: flat circumscribed pigmented patches in sun-exposed sites
  • Dermatosis papulosa nigra: small, pedunculated and heavily pigmented seborrhoeic keratoses on head and neck of darker-skinned individuals
  • Stucco keratoses: grey, white or yellow papules on the lower extremities
  • Inverted follicular keratosis
  • Large cell acanthoma
  • Lichenoid keratosis: an inflammatory phase preceding involution of some seborrhoeic keratoses and solar lentigines.

 

Diagnosis of Seborrheic Keratosis

It is difficult to identify the lesion of Seborrheic Keratosis by naked eye is difficult. The lesion is confused with warts, (pigmented) basal cell, carcinoma, pigmented Bowen’s disease, (verrucous) melanoma, extramammary Paget’s disease, common warts, acanthosis nigricans, and Seborrheic Keratosis like lesions localized to tattoo1.

Although most Seborrheic Keratosis have a maximum diameter of less than 4 cm, sometimes giant lesions develop that raise some possible differential diagnoses, including Buschke–Löwenstein tumors1.

The diagnosis of Seborrheic keratosis can be made with confidence with a high resolution dermascope, through which the lesions of Seborrheic keratosis exhibit the typical dermoscopic findings of fissures and ridges, hairpin vessels with white halo, comedo-like openings, and milia-like cysts.The histopathologic counterparts of the dermoscopic findings are papillomatous epidermis, enlarged dermal capillaries, pseudo-horn cysts, and intraepidermal cysts. Dermoscopy is of practical
value in differentiating Seborrheic keratosis from malignant melanoma1.

Diagnostic findings on dermascopy shows a disordered structure with multiple orange or brown clods (due to keratin in skin surface crevices), white milia-like clods, and curved thick ridges and furrows forming a brain-like or cerebriform pattern.

 

Dermoscopy showing fissures and ridges, sharp demarcation, and moth-eaten border5

Dermoscopy findings in Seborrheic keratosis 5
1 Comedo like openings
2 Fissures and Ridges
3   Millia like cysts
4  Sharp demarcation and network like structure
5 Moth eaten border
6 Fingerprint structures
7 Hair pin blood vessels

Seborrheic Keratosis of the genitalia is a rare entity13, 14. It has been frequently mistaken as genital warts and differentiation is made only on histopathology12.There have been reports of Human papilloma virus in the lesions of Seborrheic keratosis. Seborrheic keratoses situated in the anogenital region often resemble condylomata acuminata, clinically and histopathologically, yet they are benign neoplasms of unknown cause, in contrast to condylomata acuminata, which are hyperplasias induced by human papillomavirus (HPV). To put an end to this controversy now it is postulated that lesions which have  but these “Seborrheic Keratoses” That Contain Human Papillomavirus Are Condylomata Acuminata6. A pathogenic relationship between HPV and genital SK by showing: 1) a high rate of virus detection in these lesions, with a strong predilection for HPV6, and 2) scarcity of genital HPV types in most of the remaining non-SK cutaneous genital lesions and in the extragenital Seborrheic Keratosis. HPV cannot be found in a minority of genital Seborrheic Keratosis using highly sensitive techniques, and therefore, other presently unknown factors may also be implied in the pathogenesis of these lesions8.Thus Genital seborrheic keratoses are human papillomavirus-related lesions8. The genital lesions rather be called as seborrheic keratosis like lesions because of their relation to low risk human papilloma virus. Genital seborrheic keratosis is invariably associated with HPV infection8, 9, 13.

 

Symptoms

A seborrheic keratosis usually looks like a waxy or wartlike growth. It typically appears on the face, chest, shoulders, back, spine and groin. Seborrhoeic keratoses can arise on any area of skin, with the exception of palms and soles. They do not arise from mucous membranes. You may develop a single growth, though multiple growths are more common. They appear to stick on to the skin surface.

A seborrheic keratosis:

  • Ranges in color from light tan to brown or black, Skin coloured, yellow, grey, light brown, dark brown, black or mixed colours
  • Is round or oval shaped
  • Has a characteristic "pasted on" look
  • Is flat or slightly raised with a scaly surface, Flat or raised papule or plaque, Smooth, waxy or warty surface
  • Ranges in size from very small to more than 1 inch (2.5 centimeters) across (1 mm to several cm in diameter)
  • May itch

 

 

 

Medical Management

Ammonium lactate (Lacsoft cream) and alpha hydroxy acids have been reported to reduce the height of seborrheic keratoses.  Superficial lesions can be treated by carefully applying pure trichloroacetic acid and repeating if the full thickness is not removed on the first treatment.

The US Food and Drug Administration (FDA) approved a concentrated hydrogen peroxide 40% solution (Eskata) for adults with raised seborrheic keratosis. The solution is available within an applicator pen and is administered in a medical office setting by a healthcare professional4.HP40 may act not only through its direct oxidation of organic tissues, generation of reactive oxygen species, and local lipid peroxidation but also by the generation of local concentrations of oxygen that are toxic to Seborrheic Keratosis cells7, 10.

 

Surgical Management

 

Methods used to remove seborrhoeic keratoses include:

  • Cryotherapy (liquid nitrogen) for thinner lesions with carbon dioxide (dry ice) or liquid nitrogen,
  • Curettage and/or electrocautery / Electrodesiccation / electrodesiccation and curettage / curettage alone (If a biopsy is not desired).
  • Ablative laser surgery / dermabrasion surgery
  • Shave biopsy (shaving off with a scalpel) - Shave biopsy or excision using a scalpel, The shave biopsy provides histologic material for accurate diagnosis and removes the lesion in a cosmetically acceptable manner at the same time. After a shave biopsy is obtained, a curette can be employed to smooth and remove any remaining keratotic material.
  • Focal chemical peel with trichloracetic acid

 

Long-Term Monitoring

Follow-up for patients with multiple seborrheic keratoses is important because malignant tumors can develop elsewhere on the body (or rarely within a seborrheic keratosis). New seborrheic keratoses develop as people age. The Sign of Leser–Trélat is a rare finding of sudden eruption of seborrhoeic keratoses associated with malignancies, like gastrointestinal adenocarcinoma or melanoma15,16.

 

Differential Diagnosis of Seborrheic keratosis11

  • Acrochordon
  • Acrokeratosis Verruciformis of Hopf
  • Actinic Keratosis
  • Arsenical Keratosis
  • Basal Cell Carcinoma
  • Bowen Disease
  • Bowenoid Papulosis
  • Confluent and Reticulated Papillomatosis
  • Cutaneous Horn
  • Cutaneous Manifestations of HIV
  • Cutaneous Melanoma
  • Cutaneous Squamous Cell Carcinoma
  • Dermatosis Papulosa Nigra
  • Epidermal Nevus Syndrome
  • Epidermodysplasia Verruciformis
  • Erythroplasia of Queyrat (Bowen Disease of the Glans Penis)
  • Genital Warts
  • Guttate Psoriasis
  • Lentigo
  • Melanocytic Nevi
  • Nevus Sebaceus
  • Nongenital Warts
  • Pemphigus Erythematosus
  • Plaque Psoriasis
  • Premalignant Fibroepithelial Tumor (Pinkus Tumor)
  • Prurigo Nodularis
  • Sign of Leser-Trelat
  • Stucco Keratosis
  • Warty Dyskeratoma

 

References

  1. Wollina U. Recent advances in managing and understanding seborrheic keratosis. F1000Res. 2019 Aug 28;8:F1000 Faculty Rev-1520. doi: 10.12688/f1000research.18983.1. PMID: 31508199; PMCID: PMC6719672.
  2. Fernandes KAP, Martinez DCS, Nobre AB, Campos-do-Carmo G. Collision tumor: pigmented Bowen's disease and seborrheic keratosis. An Bras Dermatol. 2018 Sep-Oct;93(5):737-739. doi: 10.1590/abd1806-4841.20187117. PMID: 30156629; PMCID: PMC6106659.
  3. Salah B, Mahseeri M, Al-Ali Z, Gaith A, Aldwan T, Al-Rawashdeh B. Giant perianal Seborrheic keratosis: A case report. Int J Surg Case Rep. 2018;51:296-301. doi: 10.1016/j.ijscr.2018.09.001. Epub 2018 Sep 12. PMID: 30243263; PMCID: PMC6148732.
  4. Robertson S, Franko J. Hydrogen Peroxide 40% (Eskata) for Seborrheic Keratosis. Am Fam Physician. 2019 Nov 15;100(10):643-644. PMID: 31730314.
  5. Alapatt GF, Sukumar D, Bhat MR. A Clinicopathological and Dermoscopic Correlation of Seborrheic Keratosis. Indian J Dermatol. 2016 Nov-Dec;61(6):622-627. doi: 10.4103/0019-5154.193667. PMID: 27904179; PMCID: PMC5122276.
  6. Li, Juan M.D.; Ackerman, A. Bernard M.D. “Seborrheic Keratoses” That Contain Human Papillomavirus Are Condylomata Acuminata, The American Journal of Dermatopathology: August 1994 - Volume 16 - Issue 4 - p 398-405 (abstract).
  7. Baumann LS, Blauvelt A, Draelos ZD, Kempers SE, Lupo MP, Schlessinger J, Smith SR, Wilson DC, Bradshaw M, Estes E, Shanler SD. Safety and efficacy of hydrogen peroxide topical solution, 40%(w/w) in patients with seborrheic keratoses: results from two identical, randomized, double-blind, placebo-controlled, phase 3 studies (A-101-SEBK-301/302) Journal of the American Academy of Dermatology. Volume 79, Issue 5, November 2018, Pages 869-877.
  8. Tardío JC, Bancalari E, Moreno A, Martín-Fragueiro LM. Genital seborrheic keratoses are human papillomavirus-related lesions. A linear array genotyping test study. APMIS. 2012 Jun;120(6):477-83. doi: 10.1111/j.1600-0463.2011.02853.x. Epub 2012 Jan 12. (abstract).
  9. Talia KL, McCluggage WG. Seborrheic Keratosis-like Lesions of the Cervix and Vagina: Report of a New Entity Possibly Related to Low-risk Human Papillomavirus Infection. Am J Surg Pathol. 2017 Apr;41(4):517-524. PMID: 27792064. (Abstract).
  10. Wollina U. Seborrheic Keratoses - The Most Common Benign Skin Tumor of Humans. Clinical presentation and an update on pathogenesis and treatment options. Open Access Maced J Med Sci. 2018;6(11):2270-2275. Published 2018 Nov 23. doi:10.3889/oamjms.2018.460
  11.  emedicine.medscape.com Seborrheic Keratosis by Arthur K Balin, MD, Medical Director, The Sally Balin Medical Center for Dermatology.
  12. Sudhakar N, Venkatesan S, Mohanasundari PS, Thilagavathy S, Elangovan P. Seborrheic keratosis over genitalia masquerading as Buschke Lowenstein tumor. Indian J Sex Transm Dis AIDS. 2015 Jan-Jun;36(1):77-9. doi: 10.4103/0253-7184.156736. PMID: 26392661; PMCID: PMC4555906.
  13. Part M, Svecová D, Brezová D, Breza J. Giant seborrheic keratoses on penis. J Sex Med. 2014 Dec;11(12):3119-22. doi: 10.1111/jsm.12676. Epub 2014 Aug 19. PMID: 25135108. (Abstract).
  14. Thakur JS, Thakur A, Chauhan CG, Diwana VK, Chauhan DC. Giant pedunculated seborrheic keratosis of penis. Indian J Dermatol. 2008 Jan;53(1):37-8. doi: 10.4103/0019-5154.39743. PMID: 19967020; PMCID: PMC2784587.
  15. Chakradeo K, Narsinghpura K, Ekladious A. Sign of Leser-Trélat. BMJ Case Rep. 2016;2016:bcr2016215316. Published 2016 Apr 8. doi:10.1136/bcr-2016-215316.
  16. Gori N, Esposito I, Del Regno L, D'Amore A, Peris K, Di Stefani A. Leser-Trélat sign as a rare manifestation of cutaneous melanoma. Dermatol Reports. 2020;12(1):8665. Published 2020 Jul 6. doi:10.4081/dr.2020.8665
 
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