Seminars in Diagnostic Pathology
Volume 26, Issue 3 , Pages 150-163 , August 2009

Keratoacanthoma: hyperplasia, benign neoplasm, or a type of squamous cell carcinoma?

  • Joshua C. Mandrell, MD

      Affiliations

    • St. Johns Mercy Medical Center, St. Louis, Missouri
  • ,
  • Daniel J. Santa Cruz, MD, FASD

      Affiliations

    • WCP Laboratories, St. Louis, Missouri
    • Corresponding Author InformationAddress reprint requests and correspondence: Daniel J. Santa Cruz, MD, FASD, 2326 Millpark Drive, St. Louis, MO 63043

References 

  1. Rook A, Whimster IW. Le keratoacanthome. Arch Belg Dermatol Syphilol. 1950;6:137–146
  2. Rook A, Whimster I. Keratoacanthoma—A thirty year retrospect. Br J Dermatol. 1979;100:41–47
  3. Hodak E, Jones RE, Ackerman AB. Solitary keratoacanthoma is a squamous-cell carcinoma: Three examples with metastases. Am J Dermatopathol. 1993;15:332–342discussion; 343-352
  4. Alyahya GA, Heegaard S, Prause JU. Malignant changes in a giant orbital keratoacanthoma developing over 25 years. Acta Ophthalmol Scand. 2000;78:223–225
  5. Gross DA. Metastasizing keratoacanthoma?. Plast Reconstr Surg. 1979;63:258–259
  6. Grossniklaus HE, Wojno TH, Yanoff M, et al. : Invasive keratoacanthoma of the eyelid and ocular adnexa. Ophthalmology. 1996;103:937–941
  7. Goldenhersh MA, Olsen TG. Invasive squamous cell carcinoma initially diagnosed as a giant keratoacanthoma. J Am Acad Dermatol. 1984;10:372–378
  8. Choonhakarn C, Ackerman AB. Keratoacanthomas: A new classification based on morphological findings. Dermatopathol Pract Conceptual. 2001;7:
  9. Hutchinson J. The crateriform ulcer of the face: A form of acute epithelial cancer. Trans Pathol Soc London. 1889;40:275–281
  10. Gougerot H. Verrucome avec adenite, a structure epitheliomatiforme, curable par le 914. Arch Dermatol Syphiligr. 1929;1:374–385
  11. Dupont A. Kyste sébaceé atypique. Bull Soc Belg Dermatol Syphiligr. 1930;177–179
  12. Smith JF. A case of multiple primary squamous-celled carcinomata of the skin in a young man, with spontaneous healing. Br J Dermatol. 1934;46:267–272
  13. Dunn JS, Ferguson-Smith J. Self-healing primary squamous carcinoma of the skin. Br J Dermat Syph. 1934;46:519–523
  14. MacCormac H, Scarff RW. Molluscum sebaceum. Br J Dermatol. 1936;48:624–627
  15. Poth DO. Tumor-like keratoses: Report of a case. Arch Dermatol Syphilol. 1939;39:228–238
  16. Dupont A. Kystes sébacés végétans, kératoacanthomes, verrucomes. Bull Soc Fr Dermatolol Syphiligr. 1952;59:340
  17. Halnan KE. Molluscum pseudocarcinomatosum. Lancet. 1953;265:1358
  18. Marshall J, Pepler WJ. Mollusca pseudocarcinomatosa: Discussion of a case of the Ferguson-Smith type, of unilateral distribution. Br J Cancer. 1954;8:251–254
  19. Winer LH. In discussion of papers of Binkely GW, Johnson HH, and Ereaux, et al. Arch Dermatol Forsch. 1955;71:66
  20. Grinspan D, Abulafia J. Idiopathic cutaneous pseduoepitheliomatous hyperplasia. Cancer. 1955;8:1047–1056
  21. Duany NP. Squamous cell pseudoepithelioma (keratoacanthoma): A new clinical variety, gigantic, multiple, and localized. AMA Arch Derm. 1958;78:703–709
  22. Brothers WS, New WN, Nickel WR. Keratoacanthoma (A review of histopathological specimens previously diagnosed as keratoacanthoma or as squamous cell carcinoma of the skin). Arch Dermatol. 1960;81:369–372
  23. Peterkin GA, Macmillan JB, Maclean S. Pseudocarcinoma of the skin (A follow-up of cases of keratoacanthoma seen in the 10 years 1951-60). Scott Med J. 1962;7:27–35
  24. Rulon DB, Helwig EB. Cutaneous sebaceous neoplasm. Cancer. 1974;265:82–102
  25. Kwittken J. A histologic chronology of the clinical course of the keratocarcinoma (so-called keratoacanthoma). Mt Sinai J Med. 1975;42:127–135
  26. Pillsbury DM, Beerman H. Multiple keratoacanthoma. Am J Med Sci. 1958;236:614–624
  27. Epstein NN, Biskind GR, Pollack RS. Multiple primary self-healing squamous-cell ‘epitheliomas' of the skin. AMA Arch Derm. 1957;75:210–223
  28. Connors RC, Ackerman AB. Histologic pseudomalignancies of the skin. Arch Dermatol. 1976;112:1767–1780
  29. Lloyd KM, Hall JH. Ferguson Smith's syndrome of multiple keratoacanthoma. Cutis. 1969;5:1093–1097
  30. Ereaux LP, Schopflocher P, Fournier CJ. Keratoacanthoma. AMA Arch Derm. 1955;71:73–83
  31. Tobias N. Keratoacanthoma; differential diagnosis from squamous-cell carcinoma of the skin. Mo Med. 1958;55:979–980
  32. Kopf AW. Keratoacanthoma. In:  Andrade G, Popkin , Rees  editor. Cancer of the Skin: Biology, Diagnosis, Management. Philadelphia, PA: WB Saunders; 1976;p. 755–781
  33. Whittle CH, Davis RA. Keratoacanthoma of lower-lip red margin. Lancet. 1957;272:1019–1020
  34. Clendenning WE, Auerbach R. Keratoacanthomata in generalized pustular psoriasis. Acta Derm Venereol. 1963;43:68–75
  35. Elschner H. Molluscum pseudocarcinomatosum (keratoacanthoma) after trauma. Hautarzt. 1956;7:368–369
  36. Pattee SF, Silvis NG. Keratoacanthoma developing in sites of previous trauma: a report of two cases and review of the literature. J Am Acad Dermatol. 2003;48(suppl):S35–S38
  37. Bruner JM. Keratoacanthoma. Plast Reconstr Surg. 1963;31:281–288
  38. Haider S. Keratoacanthoma in a smallpox vaccination site. Br J Dermatol. 1974;90:689–690
  39. Norgauer J, Rohwedder A, Schaller J. Human papillomavirus and Grzybowski's generalized eruptive keratoacanthoma. J Am Acad Dermatol. 2003;49:771–772
  40. Shamanin V, zur Hausen H, Lavergne D, et al. Human papillomavirus infections in nonmelanoma skin cancers from renal transplant recipients and nonimmunosuppressed patients. J Natl Cancer Inst. 1996;88:802–811
  41. Saftic M, Batinac T, Zamolo G, et al. HPV 6-positive giant keratoacanthoma in an immunocompetent patient. Tumori. 2006;92:79–82
  42. Forslund O, DeAngelis PM, Beigi M, et al. Identification of human papillomavirus in keratoacanthomas. J Cutan Pathol. 2003;30:423–429
  43. Payne D, Newman C, Tyring S. Human papillomavirus DNA in nonanogenital keratoacanthoma and squamous cell carcinoma of patients with HIV infection. J Am Acad Dermatol. 1995;33:1047–1049
  44. Stockfleth E, Meinke B, Arndt R, et al. Identification of DNA sequences of both genital and cutaneous HPV types in a small number of keratoacanthomas of nonimmunosuppressed patients. Dermatology. 1999;198:122–125
  45. Hsi ED, Svoboda-Newman SM, Stern RA, et al. Detection of human papillomavirus DNA in keratoacanthomas by polymerase chain reaction. Am J Dermatopathol. 1997;19:10–15
  46. Euvrard S, Chardonnet Y, Pouteil-Noble C, et al. Association of skin malignancies with various and multiple carcinogenic and noncarcinogenic human papillomaviruses in renal transplant recipients. Cancer. 1993;72:2198–2206
  47. Moy RL, Quan MB. The presence of human papillomavirus type 16 in squamous cell carcinoma of the proximal finger and reconstruction with a bilobed transposition flap. J Dermatol Surg Oncol. 1991;17:171–175
  48. Kawashima M, Favre M, Obalek S, et al. Premalignant lesions and cancers of the skin in the general population: Evaluation of the role of human papillomaviruses. J Invest Dermatol. 1990;95:537–542
  49. Magee KL, Rapini RP, Duvic M, et al. Human papillomavirus associated with keratoacanthoma. Arch Dermatol. 1989;125:1587–1589
  50. Trowell HE, Dyall-Smith ML, Dyall-Smith DJ. Human papillomavirus associated with keratoacanthomas in Australian patients. Arch Dermatol. 1990;126:1654
  51. Scheurlen W, Gissmann L, Ikenberg H, et al. Molecular cloning of two new HPV types (HPV 37 and HPV 38) from a keratoacanthoma and a malignant melanoma. Int J Cancer. 1986;37:505–510
  52. Gassenmaier A, Pfister H, Hornstein OP. Human papillomavirus 25-related DNA in solitary keratoacanthoma. Arch Dermatol Res. 1986;279:73–76
  53. Hurt MA. Keratoacanthoma vs. squamous cell carcinoma in contrast with keratoacanthoma is squamous cell carcinoma. J Cutan Pathol. 2004;31:291–292author reply 292-293
  54. Korenberg R, Penneys NS, Kowalczyk A, et al. Quantitation of S100 protein-positive cells in inflamed and non-inflamed keratoacanthoma and squamous cell carcinoma. J Cutan Pathol. 1988;15:104–108
  55. Stephenson TJ, Nichols CE, Cotton DWK. Keratoacanthomas contain a higher density of Langerhans' cells than well differentiated squamous cell carcinomas. J Pathol. 1987;152:238A
  56. Ghadially FN. The role of the hair follicle in origin and evolution of some cutaneous neoplasm in experimental animals. Cancer. 1961;14:801–816
  57. Wade TR, Ackerman AB. The many faces of keratoacanthomas. J Dermatol Surg Oncol. 1978;4:498–501
  58. Dupont A. Kerato-acanthoma, cyst sebaceous vegetans; molluscum sebaceum. Ann Dermatol Syphiligr (Paris). 1954;81:621–633
  59. Schwartz RA. Keratoacanthoma: a clinico-pathologic enigma. Dermatol Surg. 2004;30:326–333
  60. Schwartz RA. Keratoacanthoma. J Am Acad Dermatol. 1994;30:1–19quiz 20-22
  61. Karaa A, Khachemoune A. Keratoacanthoma: A tumor in search of a classification. Int J Dermatol. 2007;46:671–678
  62. Sullivan JJ. Keratoacanthoma: The Australian experience. Australas J Dermatol. 1997;38(suppl 1):S36–S39
  63. Beham A, Regauer S, Soyer HP, et al. Keratoacanthoma: A clinically distinct variant of well differentiated squamous cell carcinoma. Adv Anat Pathol. 1998;5:269–280
  64. Griffiths RW. Keratoacanthoma observed. Br J Plast Surg. 2004;57:485–501
  65. Seifert A, Nasemann T. Keratoacanthoma and its clinical variants (Review of the literature and histopathologic analysis of 90 cases). Hautarzt. 1989;40:189–202
  66. Venkei T, Sugar J. Keratoacanthoma of precarcinomatous character keratoacanthoma A and B. Dermatol Wochenschr. 1958;138:957–965
  67. Kern WH, McCray MK. The histopathologic differentiation of keratoacanthoma and squamous cell carcinoma of the skin. J Cutan Pathol. 1980;7:318–325
  68. King DF, Barr RJ. Intraepithelial elastic fibers and intracytoplasmic glycogen: Diagnostic aids in differentiating keratoacanthoma from squamous cell carcinoma. J Cutan Pathol. 1980;7:140–148
  69. Cooper PH, Wolfe JT. Perioral keratoacanthomas with extensive perineural invasion and intravenous growth. Arch Dermatol. 1988;124:1397–1401
  70. Lapins NA, Helwig EB. Perineural invasion by keratoacanthoma. Arch Dermatol. 1980;116:791–793
  71. Calonje E, Jones EW. Intravascular spread of keratoacanthoma (An alarming but benign phenomenon). Am J Dermatopathol. 1992;14:414–417
  72. Dufresne RG, Marrero GM, Robinson-Bostom L. Seasonal presentation of keratoacanthomas in Rhode Island. Br J Dermatol. 1997;136:227–229
  73. Reed RJ. Actinic keratoacanthoma. Arch Dermatol. 1972;106:858–864
  74. Allen CA, Stephens M, Steel WM. Subungual keratoacanthoma. Histopathology. 1994;25:181–183
  75. Oliwiecki S, Peachey RD, Bradfield JW, et al. Subungual keratoacanthoma—A report of four cases and review of the literature. Clin Exp Dermatol. 1994;19:230–235
  76. Stoll DM, Ackerman AB. Subungual keratoacanthoma. Am J Dermatopathol. 1980;2:265–271
  77. Maruani A, Michenet P, Lagasse JP, et al. Keratoacanthoma of the anal margin. Gastroenterol Clin Biol. 2004;28:906–908
  78. Freedman PD, Kerpel SM, Begel H, et al. Solitary intraoral keratoacanthoma (Report of a case). Oral Surg Oral Med Oral Pathol. 1979;47:74–76
  79. Janette A, Pecaro B, Lonergan M, et al. Solitary intraoral keratoacanthoma: Report of a case. J Oral Maxillofac Surg. 1996;54:1026–1030
  80. Miedzinski F, Kozakiewicz J. Keratoacanthoma centrifugum—a special variety of keratoacanthoma. Hautarzt. 1962;13:348–352
  81. Schnitzler L, Schubert SB, Verret JL, et al. Épithéliomatose familiale de Ferguson-Smith. Ann Dermatol Venereol. 1977;104:206–216
  82. Agarwal M, Chander R, Karmakar S, et al. Multiple familial keratoacanthoma of Witten and Zak—A report of three siblings. Dermatology. 1999;198:396–399
  83. Grzbowski M. A case of peculiar generalized epithelial tumors of the skin. Br J Dermatol. 1950;62:310–313
  84. Manstein CH, Frauenhoffer CJ, Besden JE. Keratoacanthoma: Is it a real entity?. Ann Plast Surg. 1998;40:469–472
  85. Cain CT, Niemann TH, Argenyi ZB. Keratoacanthoma versus squamous cell carcinoma (An immunohistochemical reappraisal of p53 protein and proliferating cell nuclear antigen expression in keratoacanthoma-like tumors). Am J Dermatopathol. 1995;17:324–331
  86. Ledo E. Wart, keratoacanthoma, and squamous cell carcinoma: a spectrum of the same neoplastic process?. Int J Dermatol. 1992;31:777–778
  87. LeBoit PE. Is keratoacanthoma a variant of squamous cell carcinoma (New insights into an old controversysoon?). Am J Dermatopathol. 1995;17:319–320
  88. Sullivan JJ, Colditz GA. Keratoacanthoma in a sub-tropical climate. Australas J Dermatol. 1979;20:34–40
  89. Piscioli F, Boi S, Zumiani G, et al. A gigantic, metastasizing keratoacanthoma (Report of a case and discussion on classification). Am J Dermatopathol. 1984;6:123–129
  90. Schnur PL, Bozzo P. Metastasizing keratoacanthomas? (The difficulties in differentiating keratoacanthomas from squamous cell carcinomas). Plast Reconstr Surg. 1978;62:258–262
  91. Caro WA, Pronstein BR. Tumors of the skin. In:  Moschella SL,  Hurley HJ editor. Dermatology. Philadelphia, PA: WB Saunders; 1985;p. 1546
  92. Mackie RM. Epidermal skin tumors. In:  Champion RH,  Burton JL,  Ebling EJG editor. Rook/Wilkinson/Ebling Textbook of Dermatology. Oxford: Blackwell Scientific; 1992;p. 1465–1470
  93. Poleksic S, Yeung KY. Rapid development of keratoacanthoma and accelerated transformation into squamous cell carcinoma of the skin: A mutagenic effect of polychemotherapy in a patient with Hodgkin's disease?. Cancer. 1978;41:12–16
  94. Chalet MD, Connors RC, Ackerman AB. Squamous cell carcinoma vs. keratoacanthoma: Criteria for histologic differentiation. J Dermatol Surg. 1975;1:16–17
  95. Ackerman AB. Histopathology of keratoacanthoma. In:  Andrade G, Popkin , Rees  editor. Cancer of the Skin: Biology, Diagnosis, Managment. Philadelphia, PA: WB Saunders; 1976;p. 781–796
  96. Ackerman AB. Squamous-cell carcinoma vs. keratoacanthoma. J Dermatol Surg Oncol. 1982;8:418
  97. Ackerman AB, Jacobson M, Vitale P. In: Clues to Diagnosis in Dermatology. vol 59:Chicago: ASCP Publishing; 1991;
  98. Schwartz RA. The keratoacanthoma: A review. J Surg Oncol. 1979;12:305–317
  99. Kerschmann RL, McCalmont TH, LeBoit PE. p53 oncoprotein expression and proliferation index in keratoacanthoma and squamous cell carcinoma. Arch Dermatol. 1994;130:181–186
  100. Lee YS, Teh M. p53 expression in pseudoepitheliomatous hyperplasia, keratoacanthoma, and squamous cell carcinoma of skin. Cancer. 1994;73:2317–2323
  101. Putti TC, Teh M, Lee YS. Biological behavior of keratoacanthoma and squamous cell carcinoma: Telomerase activity and COX-2 as potential markers. Mod Pathol. 2004;17:468–475
  102. Sleater JP, Beers BB, Stephens CA, et al. Keratoacanthoma: A deficient squamous cell carcinoma? (Study of Bcl-2 expression). J Cutan Pathol. 1994;21:514–519
  103. Krunic AL, Garrod DR, Smith NP, et al. Differential expression of desmosomal glycoproteins in keratoacanthoma and squamous cell carcinoma of the skin: an immunohistochemical aid to diagnosis. Acta Derm Venereol. 1996;76:394–398
  104. Melendez ND, Smoller BR, Morgan M. VCAM (CD-106) and ICAM (CD-54) adhesion molecules distinguish keratoacanthomas from cutaneous squamous cell carcinomas. Mod Pathol. 2003;16:8–13
  105. Mukunyadzi P, Sanderson RD, Fan CY, et al. The level of syndecan-1 expression is a distinguishing feature in behavior between keratoacanthoma and invasive cutaneous squamous cell carcinoma. Mod Pathol. 2002;15:45–49
  106. Levy EJ, Cahn MM, Shaffer B, et al. Keratoacanthoma. J Am Med Assoc. 1954;155:562–564
  107. Brown JB, Fryer MP. Fallacy of term self-healing epidermoid carcinoma and limitations of microscopic interpretations. Surg Gynecol Obstet. 1955;100:179–183
  108. Brown J, Fryer M. The limits and inadequacies of microscopic interpretation of tumors. Plast Reconstr Surg. 1955;16:23–30

PII: S0740-2570(09)00042-2

doi: 10.1053/j.semdp.2009.09.003

Seminars in Diagnostic Pathology
Volume 26, Issue 3 , Pages 150-163 , August 2009