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Introduction

Keratoacanthoma is a relatively common, low-grade, and rapidly developing neoplasm of the epithelium. The behavioral nature of these lesions is disputed in the literature, with some sources describing keratoacanthoma as reactive, pseudomalignant processes; however, modern consensus favors description of these lesions as low grade variants of squamous cell carcinoma (SCC). Keratoacanthomas occur most frequently in older men and fair-skinned individuals, and they typically develop on sun-exposed areas like the dorsum of the hand and wrist. They are characterized by rapid growth at the outset, followed by a period of stability, then spontaneous regression in many cases. Due to their potential to persist and progress into invasive SCC, excision or other destructive treatment is often recommended.1-4

Pathophysiology

  • The definitive cause of keratoacanthoma has not yet been clearly established, but ultraviolet (UV) radiation, exposure to chemical carcinogens, immunosuppression, use of BRAF-inhibiting therapy, genetic predisposition, viral exposure and recent trauma or surgery have all been proposed as potential risk factors.3
  • Several similarities suggest a common pathogenesis between keratoacanthomas and SCCs, but in contrast to ordinary SCC, keratoacanthoma typically originate from the pilosebaceous unit of hair follicles. Within the follicles, keratoacanthomas are derived from an abnormality that leads to hyperkeratosis of the infundibulum.3,4
  • Keratoacanthomas typically develop in the following three stages:
    • Proliferative phase: rapid growth occurs for up to ~6-8 weeks
    • Maturation phase: the keratoacanthoma maintains its crateriform appearance for several weeks to months
    • Involution phase: the final stage in which the lesion regresses into an atrophic scar3

Related Anatomy

  • Dermis
  • Epidermis
  • Epithelium 
  • Infundibulum segment of follicle
  • Pilosebaceous glands
  • Keratoacanthomas can be further divided into the following subtypes:
    • Solitary keratoacanthoma
    • Subungual keratoacanthoma
    • Mucosal keratoacanthoma
    • Giant keratoacanthoma
    • Keratoacanthoma centrifugum marginatum
    • Generalized eruptive keratoacanthoma of Grzybowski
    • Multiple keratoacanthomas Ferguson-Smith syndrome3

Incidence and Related Conditions

  • The true incidence of these lesions is likely underestimated, but one study found the incidence of sporadic solitary keratoacanthoma to be 104/100,000 and 150/100,000 in Australian and Hawaiian populations, respectively.4
  • Keratoacanthomas are reported in all age groups but rarely appear before the age of 20 and have a peak incidence between 65-71 years.3,4
  • Men are affected more frequently that women, with a male-to-female ratio of 2:1. Keratoacanthomas occur primarily in fair-skinned individuals—particularly those with Fitzpatrick skin types I-III—and are rarely seen in those with darker skin.3,4
  • Grzybowski syndrome
  • Ferguson-Smith disease
  • Muir-Torre syndrome
  • SCC

Differential Diagnosis

  • Actinic keratosis
  • Amelanotic melanoma
  • Atypical mycobacterial infection
  • Cutaneous Horn
  • Deep fungal infection
  • Foreign body reaction
  • Hypertrophic lichen planus
  • Merkel cell carcinoma
  • Metastatic lesion to the skin
  • Molluscum contagiosum
  • Muir-Torre Syndrome
  • Nodular basal cell carcinoma
  • Nodular Kaposi sarcoma
  • Prurigo nodularis
  • Sporotrichosis
  • Squamous cell carcinoma
  • Ulcerative basal cell carcinoma
  • Verruca vulgaris
ICD-10 Codes
  • SKIN - MALIGNANT LESIONS: KERATOCANTHOMA (UPPER LIMB)

    Diagnostic Guide Name

    SKIN - MALIGNANT LESIONS: KERATOCANTHOMA (UPPER LIMB)

    ICD 10 Diagnosis, Single Code, Left Code, Right Code and Bilateral Code

    DIAGNOSISSINGLE CODE ONLYLEFTRIGHTBILATERAL (If Available)
    KERATOCANTHOMA (UPPER LIMB) D23.62D23.61 

    ICD-10 Reference

    Reproduced from the International statistical classification of diseases and related health problems, 10th revision, Fifth edition, 2016. Geneva, World Health Organization, 2016 https://apps.who.int/iris/handle/10665/246208

Clinical Presentation Photos and Related Diagrams
Keratoacanthoma
  • Keratoacanthoma at the base of the right thumb in a 58 y.o. male home builder.  He noted the enlarging lesion 9 weeks ago.
    Keratoacanthoma at the base of the right thumb in a 58 y.o. male home builder. He noted the enlarging lesion 9 weeks ago.
  • Keratoacanthoma of lateral left arm (arrow)
    Keratoacanthoma of lateral left arm (arrow)
  • Keratoacanthoma in 75 y.o. male dorsal ulnar base of hand (arrow)
    Keratoacanthoma in 75 y.o. male dorsal ulnar base of hand (arrow)
Symptoms
Patients typically complain about a well-defined dome-shaped and erythematous or skin-colored nodule
Lesions are usually painless but may be itchy.
The most common locations for lesions are the central face and dorsum of the hands, wrists, and arms.
Typical History

A typical patient is a 67-year-old man with Fitzpatrick skin type I. His personal exposure to UV radiation is generally unremarkable, and in most cases he reported adequately protecting his skin with sunscreen when outdoors. Three months ago, he noticed a skin-colored papule developing on the dorsum of his right hand. Over the course of four weeks, it rapidly grew to a nodule with a size of just over 1 cm, and was characterized by a well-defined dome shape with a firm core at its center. Although the lesion only caused him mild itching and appeared to stop growing, he consulted with a dermatologist for an evaluation.

Positive Tests, Exams or Signs
Work-up Options
Treatment Options
Treatment Goals
  • Identify the diagnosis accurately
  • Successful treat the lesion
Conservative
  • Although keratoacanthomas are biologically benign and often resolve spontaneously, treatment is still recommended due to their relation and similarity to SCCs. For solitary lesions, treatment decisions are dependent on its location and size. 3-5
  • Topical therapy 
    • 5% imiquimod
    • 5% 5-fluorouracil
  • Intralesional injections
    • Methotrexate 
    • Bleomycin
    • 5-fluorouracil
Operative

Surgery is considered the gold standard of care for keratoacanthomas and is typically recommended unless it is unfeasible or undesired.3-5

  • Surgical excision
    • Elliptical excision
    • Full-thickness fusiform excision 
    • No specific margins have been established for keratoacanthoma excision, but 3-5 mm margins are generally recommended, which are similar to those used in SCC.
    • Electrodessication and curettage
      • May be used on smaller lesions (<2 cm) on the extremities.
      • Must be followed by histologic evaluation.
      • Mohs micrographic surgery
        • Should be considered for larger tumors (>2 cm), recurrent tumors, and/or tumors located in cosmetically sensitive areas.
        • Radiotherapy
        • Phototherapy
Complications
  • Infection
  • Scarring
  • These lesions can progress into invasive SCC
Outcomes
  • When surgical excision is used to treat keratoacanthoma, the prognosis is usually excellent. In particular, full-thickness fusiform excision has been associated with good aesthetic outcomes and an optimal specimen for pathologists.3,4
  • Although data on conservative treatments is limited, some data support a 98% response rate with intralesional 5-fluorouracil administered at a dose of 40-75 mg weekly for 3-8 weeks.3
Key Educational Points
  • Curettage may likely be increasing the ratio of SCC:keratoacanthoma in pathology reports, as dermatopathologists may overdiagnose SCC when they do not have a full-thickness specimen.4
  • Nodules range in size from 1-2 cm and have a keratinous core in its center
  • Keratoacanthoma has recently been reclassified as SCC keratoacanthoma type, or SCC-KA.3
  • Dermatoscopy may not be sufficient to distinguish keratoacanthoma from SCC, but can be used to differentiate both of these lesions from other raised non-pigmented skin lesions.3,4
  • The best diagnostic test for these lesions is an excisional biopsy, as a shave biopsy may be insufficient to differentiate keratoacanthoma from SCC. Histopathologically, the presence of intraepidermal microabscesses and tissue eosinophilia is suggestive of a keratoacanthoma rather than an SCC.3
  • Over the past hundred years, this tumor has been reclassified and reported differently throughout literature. Before 1917, keratoacanthoma were regarded as skin cancer. In the 1920s, reports labeled the tumor as verrucae or vegetating sebaceous cyst. Between 1936 and the 1950s the lesion was labeled and reported in the literature as molluscum sebaceum.3
  • A consensus has not been reached as to whether keratoacanthomas are benign or malignant neoplasms, and experts in the field are divided. These lesions are routinely treated as cancer in the U.S., although there is little research on purported metastases but an overwhelming surplus of reports of their benign natural course.5
References

New and Cited Articles

  1. Ilyas EN, Leinberry CF, Ilyas AM. Skin cancers of the hand and upper extremity. J Hand Surg Am 2012;37(1):171-178. PMID: 22196297
  2. Marks JG, Miller JJ. Lookingbill and Marks’ Principles of Dermatology. Fifth Ed. London, New York: Saunders Elsevier; 2013.
  3. Zito PM, Scharf R. Keratoacanthoma. In: StatPearls.Treasure Island (FL) 2019.PMID: 29763106
  4. Kwiek B, Schwartz RA. Keratoacanthoma (KA): An update and review. J Am Acad Dermatol 2016;74(6):1220-1233.PMID: 26853179
  5. Savage JA, Maize JC, Sr. Keratoacanthoma clinical behavior: a systematic review. Am J Dermatopatho 2014;36(5):422-429.PMID: 24366198

Reviews 

  1. Kwiek B, Schwartz RA. Keratoacanthoma (KA): An update and review. J Am Acad Dermatol 2016;74(6):1220-1233.PMID: 26853179
  2. Savage JA, Maize JC, Sr. Keratoacanthoma clinical behavior: a systematic review. Am J Dermatopatho. 2014;36(5):422-429.PMID: 24366198
  3. James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin.12thEd. Philadelphia, PA. Elsevier, 2016.
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