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A Painless, Rapidly-growing Nodule in a 74-year-old Woman


The solitary, keratotic lesion has grown quickly over one month. Infection? Neoplasia? What else is in your differential diagnosis?

[[{"type":"media","view_mode":"media_crop","fid":"57089","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_6698009076881","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7204","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 358px; width: 438px; float: right;","title":"Figure 1.","typeof":"foaf:Image"}}]]Good luck on the quiz portion of Part 5 of this Special Report:  Non-melanoma Skin Cancer: A Primer for Primary Care. You can access the post-test for the Report at the end of this case.



A 74-year-old woman comes in for evaluation of a painless, non-warm, non-edematous, solitary 2-cm keratotic nodule on her left arm (Figure 1); it had been growing rapidly over the past month. 

Question 1: Which of the following clinical findings are helpful in making a diagnosis?

A. Solitary

B. Non-edematous

C. Rapidly growing

D. Keratotic

E. Painless

F. Non-warm

G. All of the above

Answer, discussion, and next question>>


The correct answer is G. All the above are helpful in making a diagnosis

A nodule that has grown rapidly over one month's time should lead one to consider at the top the differential diagnosis infection and neoplasia. A solitary lesion favors a diagnosis of tumor. Patients with abscesses often have folliculitis or multiple lesions. The rapid growth and keratotic nature do not exclude either infection or neoplasia, and while absence of warmth is more consistent with neoplasia than infection, not all local skin infections are warm. While abscesses tend to be painful and neoplasms tend not to be, there are neoplasms that present with pain, itch, or dysesthesia. Thus, all the findings noted are important to consider.

The patient saw her primary care doctor, who diagnosed the lesion as an abscess and prescribed an oral antibiotic for 5 days which had no effect. First-line treatment for an infected abscess is incision and drainage. The use of an antibiotic can also help clear an abscess more quickly. However, antibiotics have no effect on KAs.

Question 2: Which of the following questions might you ask the patient?

A. Did the lesion appear after skin trauma?

B. If trauma was present, did the trauma introduce a foreign body into the skin?

C. Did any pus drain out of the lesion?

D. Have you experienced folliculitis recently?

E. Do you own a fish tank?

F. Do you have a history of skin cancer?

G. All of the above

Answer, discussion, and next question>>


The correct answer is G. All the above are appropriate queries for the patient in this case.

The patient does recall trauma to the area, but is certain there was no foreign body involved before the lesion appeared, nor was there fish tank exposure. She denies folliculitis and no pus has drained from this lesion; she surrently has no other lesions. The patient does have a history of infiltrative basal cell carcinoma of the face that was treated by Moh’s micrographic surgery several years back. Of note, she has blue eyes, Fitzpatrick Type I skin, and extensive photo damage. The lesion presented on sun damaged skin.

Question 3: What is the most likely diagnosis?

A. Basal cell carcinoma

B. Bacterial abscess

C. Common wart

D. Keratoacanthoma

Answer and next question>>

The correct answer is D. Keratoacanthoma 


Question 4: What is the most typical course of keratoacanthoma?

A. Continued rapid growth with formation of annular lesion

B. Rapid growth followed by slow regression leaving a scar

C. Growth that plateaus and then stops with a static lesion

D. Rapid growth followed by necrosis

E. Rapid growth followed by involution and disappearance without a trace

Answer and next question>>


The correct answer is B. Rapid growth followed by slow regression, leaving a scar


Question 5: Which of the following is the best recommendation for treatment?

A. Intralesional methotrexate

B. Systemic retinoid

C. Radiotherapy

D. Complete excision

Answer and discussion>>


The correct answer is D. Complete excision



Atypical and controversial

Keratoacanthoma (KA) is a proliferation of atypical, highly differentiated squamous epithelia on sun-exposed skin. It is characterized by rapid growth over 4-6 weeks, followed by spontaneous regression over 4-6 months. Most lesions only grow to 1-2 cm in diameter.1 KA is believed to arise from hair follicles based on its triphasic course--proliferation, maturation, and regression--a course similar to the hair cycle.2

KAs are a controversial tumor because while the clinical course is benign, some consider it a well-differentiated variant of squamous cell carcinoma (SCC). It also can be a challenge to distinguish KA clinically and histologically from a highly differentiated SCC.1 In studies of Hawaiian and Australian populations, solitary sporadic KA has an incidence of 150 and 104/100,000 respectively.3,4 The incidence of KA is thought to be underestimated because of spontaneous regression, misdiagnosis as SCC, and underreporting.5 Solitary sporadic KA is mainly seen in patients with fair, sun-damaged skin, peaking between the ages of 65-71 years. Men are more commonly affected than women.6 While solitary lesions are most common, other rare variants include giant, grouped, multiple, subungual, mucosal, and KA centrifugum marginatum.1

A brief history of KA

In 1889, Jonathan Hutchinson first described KA as a “crateriform ulcer of the face.”7 The term “keratoacanthoma” was given in the 1940’s by Walter Freudenthal due to the distinctive acanthosis and keratosis seen in the tumor.8

On examination, a typical KA begins as a papule that rapidly enlarges and evolves into a well-circumscribed, crateriform nodule with a keratotic core. There is no pain or tenderness associated with the lesion.1 A solitary KA typically grows to 1-2 cm in diameter and 0.5 cm in thickness. In contrast, the KA centrifugum variant is multifollicular and can grow to more than 20 cm in diameter.9 Over the course of 4-6 months most KAs regress slowly, first in height then in diameter, leaving fibrosis and scarring at the base.10  Rare subtypes like subungual and mucosal KA do no involute and must be surgically removed.11,12

[[{"type":"media","view_mode":"media_crop","fid":"57091","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_701472923892","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7205","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 299px; width: 435px; float: right;","title":"Figure 2. ","typeof":"foaf:Image"}}]]An adequate skin biopsy including subcutaneous fat or total excision may be required to properly identify KA. Incomplete samples can result in an equivocal diagnosis or a diagnosis of SCC, potentially leading to overtreatment.13 Clinically and histologically, a KA has a “volcano-like” architecture that is crateriform and symmetric (Figure 2).

On histology, well-differentiated keratinocyte proliferation is composed of brightly eosinophilic cells with glassy cytoplasms surrounding a cornified plug.14 Inflammatory infiltrate of lymphocytes and eosinophils often is present with small intratumoral abscesses of neutrophils.10 Atypical cytology is minimal in KAs. Hyperchromatic nuclei and abnormal mitoses would be diagnostic for invasive KA-like SCC.15 Many of the findings histologically overlap with SCC. Similarly, there are no immunohistochemical markers that are unique to and reliably distinguish KA from SCC.16

Next page: Pathogenesis>>

Pathogenesis of KAs is most strongly linked to ultraviolet exposure, both natural and artificial. KA has also been linked to16

  • Immunosuppression
  • Radiation
  • Trauma (eg, tattoos)
  • Surgical procedures
  • Chemical exposure, like tar, and hyaluronic acid, acrylic hydrogel, and collagen fillers

Patients treated with BRAF inhibitors and imiquimod have been known to develop KAs as a side effect, however imiquimod has also been used successfully to treat the lesions.17,18  While no single gene has been linked to solitary sporadic KA, a p53 mutation and/or p53 protein overexpression has been found. This is a signature for ultraviolet damage, which is seen in SCC as well.19, 20

Several syndromes have been described with the occurrence of multiple KAs.


Although KAs spontaneously involute, they tend to leave an unsightly atrophic scar. Furthermore and more importantly, they are histologically difficult to differentiate from a SCC. There are reported cases of KA metastasis, but some argue these could have been SCC misdiagnosed as KA.22 Consequently, the gold standard for KA treatment is excision or Moh’s surgery, with Moh’s reserved for large lesions and those in anatomically sensitive areas.1 For multiple KAs, systemic retinoids are first-line therapy and can be combined with surgery.23 Other forms of treatment include intralesional chemotherapy, cryotherapy, imiquimod, radiotherapy and IFN-alpha-2b therapy in patients who are not suitable candidates for excision.16,24


Continue to the POST-TEST for Non-melanoma Skin Cancer: A Primer for Primary Care


Click on links below for previous sections of this Special Report, Non-melanoma Skin Cancer: A Primer for Primary Care

Part 1: Introduction and Pre-test

Part 2: A Pearly-pink Lesion on a 68-year-old Woman's Face

Part 3: Three Suspicious Lesions on an Elderly Woman's Face

Part 4: Actinic Keratosis and Squamous Cell Carcinoma: Photodamage in Progress





1.           Bolognia, J., Dermatology. 3rd ed. Vol. 2. 2012, Philadelphia: Elselvier Saunders.

2.           Ramselaar, C.G., E.J. Ruitenberg, and W. Kruizinga, Regression of induced keratoacanthomas in anagen (hair growth phase) skin grafts in mice. Cancer Res, 1980. 40(5): p. 1668-73.

3.           Reizner, G.T., et al., Basal cell carcinoma and keratoacanthoma in Hawaiians: an incidence report. J Am Acad Dermatol, 1993. 29(5 Pt 1): p. 780-2.

4.           Sullivan, J.J., Keratoacanthoma: the Australian experience. Australas J Dermatol, 1997. 38 Suppl 1: p. S36-9.

5.           Carr, R.A. and J.P. Houghton, Histopathologists' approach to keratoacanthoma: a multisite survey of regional variation in Great Britain and Ireland. J Clin Pathol, 2014. 67(7): p. 637-8.

6.           Schwartz, R.A., Keratoacanthoma: a clinico-pathologic enigma. Dermatol Surg, 2004. 30(2 Pt 2): p. 326-33; discussion 333.

7.           Hutchinson, J., The crateriform ulcer of the face: A form of epithelial cancer. Trans Pathol Soc London, 1889. 40: p. 275-281.

8.           Rook, A. and I. Whimster, Keratoacanthoma--a thirty year retrospect. Br J Dermatol, 1979. 100(1): p. 41-7.

9.           Miedzinski, F. and J. Kozakiewicz, [Keratoacanthoma centrifugum--a special variety of keratoacanthoma]. Hautarzt, 1962. 13: p. 348-52.

10.         Schwartz, R.A., Keratoacanthoma. J Am Acad Dermatol, 1994. 30(1): p. 1-19; quiz 20-2.

11.         Perrin, C., Tumors of the nail unit. A review. Part II: acquired localized longitudinal pachyonychia and masked nail tumors. Am J Dermatopathol, 2013. 35(7): p. 693-709; quiz 710-2.

12.         Svirsky, J.A., P.D. Freedman, and H. Lumerman, Solitary intraoral keratoacanthoma. Oral Surg Oral Med Oral Pathol, 1977. 43(1): p. 116-22.

13.         Dąbska, M., and A. Madejczykowa. , "Rogowiak kolczastokomórkowy–keratoacanthoma (molluscum sebaceum, molluscum pseudocarcinomatosum). Studium patologiczno-kliniczne.". Nowotwory 1959. 9: p. 1-23.

14.         Wade, T.R. and A.B. Ackerman, The many faces of keratoacanthomas. J Dermatol Surg Oncol, 1978. 4(7): p. 498-501.

15.         Gleich, T., et al., Keratoacanthoma: a distinct entity? Exp Dermatol, 2016. 25(2): p. 85-91.

16.         Kwiek, B. and R.A. Schwartz, Keratoacanthoma (KA): An update and review. J Am Acad Dermatol, 2016. 74(6): p. 1220-33.

17.         Sharma, A., et al., Vemurafenib: targeted inhibition of mutated BRAF for treatment of advanced melanoma and its potential in other malignancies. Drugs, 2012. 72(17): p. 2207-22.

18.         Pini, A.M., et al., Eruptive keratoacanthoma following topical imiquimod for in situ squamous cell carcinoma of the skin in a renal transplant recipient. J Am Acad Dermatol, 2008. 59(5 Suppl): p. S116-7.

19.         Watanabe, I.C., et al., Keratoacanthoma and Keratoacanthoma-Like Squamous Cell Carcinoma: Similar Morphology but Different Pathogenesis. Medicine (Baltimore), 2015. 94(23): p. e934.

20.         McFeat, G.D., S.L. Allinson, and T.J. McMillan, Characterisation of the p53-mediated cellular responses evoked in primary mouse cells following exposure to ultraviolet radiation. PLoS One, 2013. 8(9): p. e75800.

21.         Witten, V.H. and F.G. Zak, Multiple, primary, self-healing prickle-cell epithelioma of the skin. Cancer, 1952. 5(3): p. 539-50.

22.         Mandrell, J.C. and D. Santa Cruz, Keratoacanthoma: hyperplasia, benign neoplasm, or a type of squamous cell carcinoma? Semin Diagn Pathol, 2009. 26(3): p. 150-63.

23.         Street, M.L., J.W. White, Jr., and L.E. Gibson, Multiple keratoacanthomas treated with oral retinoids. J Am Acad Dermatol, 1990. 23(5 Pt 1): p. 862-6.

24.         Martorell-Calatayud, A., et al., [Intralesional infusion of methotrexate as neoadjuvant therapy improves the cosmetic and functional results of surgery to treat keratoacanthoma: results of a randomized trial]. Actas Dermosifiliogr, 2011. 102(8): p. 605-15.

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