- Email: [email protected]
Keratoacanthoma observed
The British Association of Plastic Surgeons (2004) 57, 485–501
Keratoacanthoma observedq Richard W. Griffiths Department of Plastic Surgery, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK Received 13 November 2003; accepted 1 May 2004
KEYWORDS Keratoacanthoma; Observation; Photographic record; Spontaneous involution
Summary Conventional advice for managing suspected keratoacanthoma is total excision because of concern that the lesion may be a squamous cell carcinoma and histological differentiation of the two lesions is difficult. Only isolated cases have been published where lesions have been observed, with photographic documentation, to spontaneous resolution. Over 11 years (1992 – 2002) the author made a primary clinical diagnosis of solitary keratoacanthoma in 19 patients based upon the history and lesion appearance. Two thigh skin graft donor site lesions, and one on the nose and one on the lower lip were excised when there was concern about their growth pattern. A fifth patient was not content to be observed and had the lesion curetted by an oncologist. The remaining 14 patients had observed lesions photographed sequentially until resolution. The commonest single site affected was the hand (five cases). The mean age was 65 years (42 – 86 years). The mean duration of the lesion at presentation was 9 weeks (4 –28 weeks), and the mean time to resolution from appearance was 27 weeks (12 –64 weeks). Mean follow-up after resolution was 3 years 5 months (range 9 months – 8 years). No recurrences occurred. No scar revisions were necessary. Claims that resolved keratoacanthomas leave poor quality scars that may need surgical revision, were not confirmed in this illustrated series which is the largest published to date. The principles of observational management are outlined and the natural history of the condition and patterns of spontaneous resolution described. Q 2004 Published by Elsevier Ltd on behalf of The British Association of Plastic Surgeons.
Although it is recognised that the condition called keratoacanthoma or molluscum sebaceum may regress spontaneously, 1,2 an overwhelming majority of authors advocate complete excision of the lesion, maintaining that either it may be an invasive squamous cell carcinoma, or that if left to involute it will leave a poor quality scar that may require surgical revision.3 – 21 In nearly 1000 pubq
This work was presented at the Summer Meeting of the British Association of Plastic Surgeons, Celtic Manor Hotel, Newport, Wales. Friday 4th July 2003. E-mail address: [email protected]
lished cases, only some 20% of lesions have been observed through to spontaneous regression,2,4,5,14, 16,22 – 34 and of all these putative keratoacanthomas, less than 2% (15 lesions) have been documented to regression with serial photographs16,22,24 – 27,29 – 34 (Table 1). Whilst there is only one report of keratoacanthoma recurring after spontaneous regression alone,35 it is established that the lesion can ‘recur’ after various types of surgical excision or other intervention during the phase of proliferation.24, 35 – 37,38 – 41 Such ‘recurrences’ occur swiftly within a few weeks and affect 3 – 8% of cases,17 and some
S0007-1226/$ - see front matter Q 2004 Published by Elsevier Ltd on behalf of The British Association of Plastic Surgeons. doi:10.1016/j.bjps.2004.05.007
486
R.W. Griffiths
Table 1 Published cases with serial photographs Author
Year
Fouracres and Whittick Calnan and Haber Thomson Peterkin et al. Rook and Champion Stranc and Robertson Wolinsky et al. Lucente Popkin Platt and Griffiths de Visscher et al. Saito et al.
1951 1955 1958 1962 1963 1979 1981 1985 1990 1995 1996 2003
Total
Lesions followed to resolution with sequential photography 1 1 1 1 1 3 1 1 1 2 1 1 15
authors have advocated that such ‘recurrences’ should lead to reclassification of the original lesion as squamous cell carcinoma.26,42,43 That such ‘recurrences’ are likely to represent a reactive process in the phase of proliferation rather than neoplastic change may be supported by the rarity of true local recurrence of invasive squamous cell carcinoma after complete excision.44 Because of the sparse documentation of the natural history and pattern of clinical regression in keratoacanthoma, the experience of one clinician was reviewed who had over more than 15 years maintained an observation policy for suspected keratoacanthoma, usually without prior biopsy, and with comprehensive follow-up. The patterns of proliferation and regression are described.
Materials and methods The author reviews his photographic records for all consecutive patients seen as outpatients with the clinical diagnosis of keratoacanthoma from 1992 to 2002, and the notes retrieved (this cohort did not include two previously reported cases32). Information was recorded of names, hospital numbers, dates of birth, date at presentation, length of history of the genesis of the lesions, and time to Table 2 Principles of management by observation Initial question—has the growth plateaued and is the lesion regressing No biopsy Close personal follow-up every 2 weeks Photograph at each attendance Be prepared to excise if patient and/or surgeon are concerned at growth pattern i.e. failure to regress
Figure 1 (A) Male age 48 years. Split thickness donor site thigh lesion present for 6 weeks. (B) Male age 69 years. Split thickness donor site thigh lesion present 11 weeks.
resolution and discharge from the follow up clinic. All photographic prints and transparencies were reviewed. Criteria for making a diagnosis of keratoacanthoma were a short history of a few weeks, and that the lesion had been larger, had reached a plateau and was now getting smaller, and the appearance of raised edges with a central keratin plug progressively fragmenting to leave a crater appearance, with or without hair growth in it. Biopsy was avoided (although some had been biopsied prior to referral) (Table 2). The clinical diagnosis of keratoacanthoma would not be entertained in the immuno-compromised patient, and in this group any new skin lesion would be excised. The management policy was to review patients
Keratoacanthoma observed
487
Figure 2 Male age 58 years. Initial lesion present 6 weeks nasal dorsum, then shown at 7 and 9 weeks, final view after excision and full thickness skin grafting.
every 2 weeks until resolution was confirmed, with photographs taken at each attendance. The same clinician saw all patients at all visits, with the exception of one patient who was seen sequentially by a consultant colleague and also seen by the author. Thus there was continuity with regard to recall for the last clinic appearance of the lesions, whether or not the immediately previous photograph was available. Patients were advised at the outset that if they preferred excision this would be
done, but they were warned that the scar quality could not be predicted. They were also counselled that ‘recurrence’ could occur if excision was performed in the phase of proliferation. Patients were advised that excision could be performed at any stage if they (or the surgeon) were unhappy about the pattern of resolution or growth, primarily lack of evidence of regression. If the ‘watch and wait policy’ was breached by some surgical intervention this was recorded.
Figure 3 Female age 57 years. Sequential views of lesion right lower lip, 5, 13 weeks after initial appearance, views after curettage and cautery 21 and 26 weeks after initial presentation.
488
Table 3 Excised lesions when observation curtailed Sex
Age prior treatment
Time of biopsy after lesion appeared (weeks)
Site
Hospital
Pathologist
Histological report
M M
48 None 69 None
None None
Thigh donor site Thigh donor site
X X
A B
M
58 Biopsy well differentiated squamous cell carcinoma
4 weeks
Nose
X
C
F
57 None
None
Lower lip
X
D
Invasive well differentiated squamous cell carcinoma Well differentiated squamous cell carcinoma considered but judged fully excised keratoacanthoma Squamo-proliferative lesion some features of keratoacanthoma but indistinguishable from invasive well differentiated squamous cell carcinoma Squamo-proliferative lesion, differentiation of keratoacanthoma from well differentiated squamous cell carcinoma cannot be made by histology alone
Table 4 Patient characteristics Growth pattern Previous intervention
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Regressing Proliferating Unsure Static Regressing Regressing Regressing Regressing Regressing Static Regressing Static Regressing Static
M M F M F M M M F M F M M M
83 42 61 66 51 52 57 75 86 70 50 74 72 80
No Paint spray Spectacles No No No Paraffin/work No No No No No Pinched on metal Rotivator injury
History (weeks) Site
No 8 Curette/cautery at 5/7 weeks 7 No 7 No 6 Biopsy at 4 weeks 11 No 28 No 8 Biopsy at 2 weeks 12 No 6 No 8 No 6 No 4 Biopsy 5 weeks 8 No 8
Cheek Nose Nose Lower lip R hand R hand R hand Eyebrow Upper lip Cheek Alar base Nose R hand R ring finger
Time to resolution (weeks) Follow-up years/months 16 19 15 16 31 48 28 64 26 16 32 12 23 24
6 year 9 months 8 year 6 year 10 months 4 year 10 months 4 year 3 year 10 months 3 year 8 months 2 year 7 months 2 year 2 months 2 year 4 months 1 year 7 months 1 year 1 months 9 months 11 months
R.W. Griffiths
Number Sex Age (years) Previous trauma
Keratoacanthoma observed
489
Figure 4 Male age 75 years. Right eyebrow lesion biopsied (prior to referral) 2 weeks after first appearance, views 12, 21, 39 and 64 weeks after initial appearance.
Patients and their general medical practitioners were contacted during 2003 to determine if the lesion had recurred after discharge from clinic follow-up. Scar quality was assessed by visual inspection by patient and surgeon. Patients’ written consent was obtained to use their photographs as illustrations, and for the one patient who died (of unrelated cause) nearly 7 years after lesion resolution his wife’s written consent to use the photographs was obtained. Table 5 Anatomical sites of lesions Site of lesions
14 Patients
Right hand Nose Cheek Lower lip Upper lip Eyebrow
5 4 2 1 1 1
Results Over the 11 year period the author made a confident primary clinical diagnosis of keratoacanthoma in 19 patients based upon the history and lesion appearance. Two thigh skin graft donor site lesions (Fig. 1(A) and (B)), and one on the nose (Fig. 2) and one on the lower lip (Fig. 3) were excised when there was subsequent concern about their growth pattern and specifically lack of sustained regression. The histological reports for these four lesions are given (Table 3). A fifth patient elected to have the lesion curetted by an oncologist. The remaining 14 patients had observed lesions photographed sequentially until resolution (Figs. 4 – 17). The quality of resultant scars after spontaneous regression is well illustrated for the various anatomical sites. A summary of comparative patient data is given (Table 4). Eight patients gave
490
R.W. Griffiths
Figure 5
Female age 86 years. Upper lip lesion views 6, 10, 14 and 29 weeks after initial appearance.
a history of the lesion getting smaller, four indicated growth had stopped, one lesion was proliferating (patient 2, Fig. 12) and one patient was not sure about the growth pattern. Male:female ratio was 10:4. Fourteen of the patients were referred from dermatologists. The commonest single affected site was the hand (five cases), (Table 5). Possible irritation from chemical or mechanical trauma was recorded for five patients with 3/5 having lesions on the hand. The mean duration of the lesion at presentation was 9 weeks (4 – 28 weeks), the mean age was 65 years (42 – 86 years) and the mean time to resolution from appearance was 27 weeks (12 – 64 weeks). The patient observed to 64 weeks was advised in writing at 20 weeks that the surgeon considered lesion excision appropriate when he felt resolution was too slow but the patient declined. This patient subsequently had longer intervals between visits and was seen on nine occasions over the observation period. Only four patients had a biopsy or curettage elsewhere before referral, all others were simply observed. The histological findings for these are given in Table 6. The times to resolution for those
biopsied were 19, 23, 31 and 64 weeks (mean 34 weeks). For those not biopsied the resolution time ranged 12 – 48 weeks (mean 23 weeks). Patients tolerated follow-up well once they saw the lesion getting smaller. Mean follow-up after regression was 3 years 5 months (range 9 months –8 years), with only two patients having less than 1 year of follow-up — 9 and 11 months, respectively. No recurrences have occurred. No scars were revised surgically and all scars were acceptable to the patients.
Discussion Since the widespread recognition of keratoacanthoma as a clinical entity some 50 years ago,23 there has been a vigorous debate about the advisability and desirability of observing lesions clinically diagnosed as keratoacanthoma. The diagnosis can be made on the short history, with a plateau of growth, and usually some definite resolution/involution noted by the patient, coupled with the appearance of the lesion which may contain hair,32 and a central keratin plug and signs
Keratoacanthoma observed
Figure 6 Male age 66 years. Lower lip lesion views 6, 8, 10 and 17 weeks after initial appearance.
Figure 7 Male age 83 years. Right cheek lesion views 12 and 20 weeks after initial appearance.
491
492
Figure 8 Male age 70 years. Right cheek/eyelid lesion views 8, 11 and 16 weeks after initial appearance.
of fragmentation and generally an appearance unlike that of a typical squamous cell carcinoma. The experience of the clinician is crucial. In this series, eight lesions had a clear history of regression, and four had stopped growing and had reached a plateau. That keratoacanthomas can spontaneously regress is well recognised,1,2,25,26,29,32,45 with Musso1 noting that after a one third biopsy there could be further growth before regression. Bruner,46 however, counselled against biopsy as being misleading and advocated excising the whole lesion. Rook and Champion27 reported that excision Table 6 Prior biopsy for observed lesions Sex
Age
Prior treatment
Time of biopsy after lesion appeared (weeks)
Site
Hospital
Pathologist
Histological report
M
42
Curette/cautery biopsy
Nose
F
51
Biopsy
5 weeks 7 weeks 4 weeks
Hand
Y Y Y
E F E
M
75
Biopsy
2 weeks
Eyebrow
Z
G
M
72
Biopsy
5 weeks
Hand
Z
H
Keratoacanthoma incompletely excised Well differentiated squamous cell carcinoma Squamo-proliferative hyper-keratotic lesion—insufficient for assessment for either keratoacanthoma or well differentiated squamous cell carcinoma Keratoacanthoma and squamous cell carcinoma cannot be distinguished reliably on this material Squamo-proliferative lesion cannot be distinguished between pseudo-carcinoma and neoplasia including well differentiated squamous cell carcinoma and keratoacanthoma
R.W. Griffiths
Keratoacanthoma observed
Figure 9
493
Female age 50 years. Left alar base lesion, views 6, 15 and 33 weeks after initial appearance.
of the lesion in the growth phase can be followed by ‘recurrence’ although more accurately this could be described as continuing growth prior to involution. Whilst some authors consider this regression to have an immunological basis,47 – 49 others have failed to demonstrate an immune effect.50,51 Keratoacanthoma can continue to regrow or ‘recur’ after various interventions, including Mohs’ surgery.14,27,35,36,38 – 41,52, and this may be more likely if ablation of the lesion has been incomplete such as with curettage (Fig. 12).The rates of recurrence have been given as 3 – 8%.17,37,53 Occasionally such ‘recurrences’ may be protracted and resistant to multi-modal treatment.54 Such ‘recurrences’ are evident within a few weeks of biopsy or other intervention such as curettage and probably represent a recrudescence of the phase of proliferation which the initial treatment did not abort.37 This is dramatically shown in Fig. 12 from the present series where there was continued growth for 20 – 30 days after two episodes of curettage and biopsy elsewhere prior to regression starting. If, however, such ‘recurrences’ occur months later then it will be wise to question the initial diagnosis, and consider if the lesion was a squamous cell carcinoma.42,43 Further reassurance should be drawn from the observation that local recurrence of invasive squamous cell carcinoma after conventional complete excision surgically and histologically is extremely rare and when recurrence does occur in some 7% it is as regional lymph node metastases.44 Only a single case report of ‘recurrence’ has been identified when spontaneous resolution has been just that, with neither prior biopsy or any other form of intervention.35 Several authors have advocated excision of keratoacanthomas claiming that spontaneous regression in their experience produces poor quality scars.4,19,26,55 – 57 Several of these authors also reasonably argue that the
patient should not have to tolerate the lesion over the course of its natural history to regression. In the present series though a majority of the cases illustrated if excised, could well have required skin grafting (including the hand lesions), and in other cases in more cosmetically sensitive areas (Figs. 8, 11 and 12) it could be persuasively argued that surgical excision and repair would have given a poorer result than that observed after spontaneous regression. Patients were generally very tolerant of the observation policy once they knew the likely consequences of surgical excision. It would be reasonable, however, to question the necessity for follow-up, as frequently as every 2 weeks, and from the experience of this study in which no lesions observed to resolution recurred, then follow-up every 4 weeks if there is evidence of sustained regression may well be adequate. The longer the follow-up interval the greater the need to impress upon the patient, the need to return immediately if the lesion enlarges. If the conservative approach is adopted it must be followed with a degree of circumspection as emphasised by Jackson8, in case the clinical diagnosis is in error and the lesion represents an enlarging squamous cell carcinoma. The principles of management must include a single senior clinician observing the patient from presentation to lesion resolution, and the lesion photographed every 2 –3 weeks. The key point in the history is a lesion diminishing in size or at least one that has stopped enlarging. The patient must be advised of the likely time scale to resolution (over 6 months on average as we have found), and also understand that at any time, if they wish, the lesion can be excised, but that the price of such surgical intervention may be an inferior cosmetic result. Advice on the possibility of ‘recurrence’ if excised in the phase of proliferation must also be given. The
494
R.W. Griffiths
Figure 10 Female age 61 years. Nasal dorsum lesion, views 7, 12, 13 and 16 weeks after initial appearance.
Keratoacanthoma observed
Figure 11
Male age 74 years. Nasal dorsum lesion views 4, 6, 10 and 13 weeks after initial appearance.
495
496
R.W. Griffiths
Figure 12 Male age 42 years. Left alar lesion, biopsied and curetted (prior to referral) 5 weeks after initial appearance; views 7, 9, 11, 19 and 32 weeks after initial appearance.
patient must clearly acknowledge that defaulting from follow-up is not an option. In the present series, there were no local recurrences or node metastases observed in the mean follow-up period of 3 years 5 months, with only two patients at present having less than 12 months follow up (11 and 9 months). The aetiology of keratoacanthoma is unclear. It can be induced experimentally in rabbits,58 and it has been described in humans to follow after 29 years of chronic irritation in the tar industry.59 Haws et al.43 described 11 –16% of keratoacanthomas to occur on the hand. With the single largest number of lesions in our series occurring on the hand, trauma may be important in some cases,60 as with its description in relation to healing skin graft donor sites and burns61 – 66 and after chemical skin
peeling. 67 It maybe that some of the acute squamous cell carcinomas described in skin graft donor sites and burn scars are in fact keratoacanthomas.68 – 72 If keratoacanthomas in fact represent well differentiated squamous cell carcinomas which spontaneously regress, then this behaviour may illustrate one end of the spectrum of behaviour of neoplasia within which spontaneous regression of malignancy is well described.49,73 – 78 Where there is real doubt regarding the clinical differentiation of keratoacanthoma from rapidly growing squamous cell carcinoma, excision is advocated.79,80 I believe this particularly holds true for skin lesions arising in immuno-compromised patients and I would not be prepared to observe lesions in
Figure 13 Male age 52 years. Right hand dorsum lesion, views 24, 29 and 35 weeks after initial appearance.
Keratoacanthoma observed
497
Figure 14 Female age 51 years. Right hand dorsum lesion, biopsied (prior to referral) 4 weeks after initial appearance, views 11, 14, 22 and 31 weeks after initial appearance.
Figure 15 Male age 72 years. Right hand dorsum lesion, views 10, 12, 23 and 30 weeks after initial appearance.
498
R.W. Griffiths
Figure 16 Male age 57 years. Right hand dorsum/base middle finger lesion, views 8, 11, 13 and 31 weeks after initial appearance.
these patients. Also if a patient is judged likely to be noncompliant with the strict follow-up regime, then it will be wiser to excise any suspicious lesions. The histological differentiation of keratoacanthoma from invasive squamous cell carcinoma is not easy, and this is clearly demonstrated in the histopathology reports from eight separate pathologists in three different hospitals given in Tables 3 and 6. Whilst some authors consider the histological and cytological differentiation precise, sure and possible,48,81 – 84 others regard the two conditions as representing a range of neoplastic activity with no clear distinction.6,8,9,11,13,85 – 88 The differential diagnosis of the two conditions is difficult not only with conventional histology,49 but also with more sophisticated techniques,89 – 91 although in one recent case of keratoacanthoma a specific chromosome aberration has been described.92 If there is medico-legal concern about observation of presumptive keratoacanthomas, after biopsy fails to exclude squamous cell carcinoma, then this must be set against the genuine histological difficulties of differentiating the two lesions after which close clinical observation becomes one legitimate option for management. LeBoit93 has written ‘no one has done a double-blind study, in
which keratoacanthoma either diagnosed by clinical appearance or by partial biopsy, have been allowed to play out their life histories’, and suggested the topic as a wonderful research opportunity ‘for young energetic dermatopathologists who bemoan the fact that the ‘old guys’ got all the good stuff, here is something to keep you occupied. Figure out the mechanism by which keratoacanthoma regresses, and see if it can be applied to other neoplasms. There might be a trip to Stockholm in it!’ Cribier et al.87 in consideration of 296 cases wrote ‘many of the criteria commonly used for the differential diagnosis of squamous cell carcinoma and keratoacanthoma are not reliable. The combination of the five most useful criteria does not significantly increase the specificity or sensitivity of the histological diagnosis in difficult cases. Atypical or difficult cases should, therefore, be considered and treated as squamous cell carcinoma since a clear cut distinction is not possible even with the aid of the most relevant criteria’. There are other treatments for keratoacanthoma, apart from surgical excision—curettage, cryotherapy, electrodessication, irradiation, 5 FU and steroids,94 – 96 but the efficacy of these therapies
Keratoacanthoma observed
499
warned of this possibility—and the surgeon not surprised when this sometimes happens. It may be that Schwartz’s concept is helpful when he concluded that keratoacanthoma is an abortive malignancy that rarely progresses into invasive squamous cell carcinoma.97
Acknowledgements I am very pleased to thank my colleague David Dujon for agreement to report on one patient with the lesion of the finger (Fig. 17). I am also most grateful to Robert Salthouse for his skill in producing the various illustrations for this paper.
References
Figure 17 Male age 80 years. Right index finger lesion, views 8, 12 and 24 weeks after initial appearance.
will of course remain unclear if used on lesions which the present study has demonstrated are consistently capable of spontaneous regression. The present series did not rely on histopathological interpretation and represents a precise clinical study of the behaviour of lesions clinically diagnosed as keratoacanthoma. Whilst for convenience of patient and surgeon the decision may be frequently taken to excise such lesions early, this should be done in the full knowledge that if some of these are treated in the phase of proliferation they may continue to grow, and patients should be
1. Musso L. Spontaneous resolution of molluscum sebaceum. Br J Dermatol 1951;63:151—3. 2. Rook A, Whimster I. Le kerato-acanthome. Arch Belges Dermatol Syph 1950;6:137—46. 3. Hutchinson J. Morbid growths and tumours 1. The crateriform ulcer of the face, a form of acute epithelial cancer. Trans Path Soc 1889;40:275—81. 4. Beare JM. Molluscum sebaceum. Br J Surg 1953;41:167—72. 5. Hueston JT. Molluscum sebaceum. Aust N Z J Surg 1956;26: 25—31. 6. Middleton AG, Curtin JW. Keratoacanthoma or squamous cell carcinoma. A surgeon’s dilemma. Plast Reconstr Surg 1966; 38:56—63. 7. Garrett WS, Ware JL, Thorne FL. Keratoacanthoma. Arch Surg 1967;94:853—7. 8. Jackson IT. Diagnostic problem of keratoacanthoma. Lancet 1969;1:490—2. 9. Neuman Z, Giladi A. Plea for a radical approach in so-called keratoacanthoma of the eyelid. Plast Reconstr Surg 1971; 47:231—3. 10. Cohen N, Plaschkes Y, Pevzner S, Loewenthal M. Review of 57 cases of keratoacanthoma. Plast Reconstr Surg 1972;49: 138—42. 11. Iverson RE, Vistnes LM. Keratoacanthoma is frequently a dangerous diagnosis. Am J Surg 1973;126:359—65. 12. Schnur PL, Bozzo P. Metastasising keratoacanthomas ? Plast Reconstr Surg 1978;62:258—62. 13. Sanders GH, Miller TA. Are keratoacanthomas really squamous cell carcinomas ? Ann Plast Surg 1982;9:306—9. 14. Kingman J, Callen JP. Keratoacanthoma. Arch Dermatol 1984;120:736—40. 15. Stal S. Keratoacanthoma. Clin Plast Surg 1987;14:423. 16. Popkin GL. Tumors of the skin: a dermatologist’s viewpoint. In: Mc Carthy JG, editor. Plastic surgery. Tumors of the head and neck and skin, vol. 5. Philadelphia: WB Saunders; 1990; p. 3560—613. 17. Goslen JB. Chapter 55, Management of keratoacanthomas, in Wheeland RG ed, Cutaneous Surgery. Philadelphia: WB Saunders; 1994, p. 723—30. 18. Schwartz RA. Keratoacanthoma. J Am Acad Dermatol 1994; 30:1—19. 19. Burns T. Recognising and managing keratoacanthoma. Practitioner 1997;241:424.
500
20. Manstein CH, Frauenhoffer CJ, Besden JE. Keratoacanthoma: is it a real entity ? Ann Plast Surg 1998;40: 469—72. 21. Ghadially R, Ghadially FN. Chapter 82, Keratoacanthoma, in Freedberg IM, et al., editors. Fitzpatrick’s dermatology in general medicine 5th edn. New York: McGraw Hill; 1999, p. 865—72. 22. Fouracres FA, Whittick JW. The relationship of molluscum sebaceum (keratoacanthoma) to spontaneous healing epithelioma of the skin. Br J Cancer 1953;7:58—64. 23. Levy EJ, Shaffer B, Beerman H. Keratoacanthoma. JAMA 1954;155:562—4. 24. Calnan CD, Haber H. Molluscum sebaceum. J Path Bact 1955; 69:61—6. 25. Thomson S. Molluscum sebaceum and its surgical signficance. Ann Roy Coll Surg Engl 1958;22:382—400. 26. Peterkin GAG, MacMillan JB, MacLean S. Pseudo-carcinoma of the skin. A follow up of cases of keratoacanthoma seen in the 10 years 1951—1960. Scot Med J 1962;7:27—35. 27. Rook A, Champion RH. Keratoacanthoma. NCI Monographs 1963;10:257—73. 28. Rank BK, Dixon PL. Another look at keratoacanthoma. Aust N Z J Surg 1979;49:654—8. 29. Stranc MF, Robertson GA. Conservative treatment of keratoacanthomas. Ann Plast Surg 1979;2:525—30. 30. Wolinsky S, Silvers DN, Kohn SR, Sanders SL, Herman EW. Spontaneous regression of a giant keratoacanthoma. Photographic documentation and histopathologic correlation. J Dermatol Surg Oncol 1981;7:897—901. 31. Lucente FE. Giant keratoacanthoma of the nose. Otolaryngol Head Neck Surg 1985;93:112—6. 32. Platt AJ, Griffiths RW. Keratoacanthoma: the value of photographic follow-up in conservative management. Eur J Plast Surg 1995;18:85—7. 33. De Visscher JGAM, van der Wal JE, Starink ThM, Tiwari RM, van der Wal I. Giant keratoacanthoma of the lower lip. Report of a case of spontaneous regression. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:193—6. 34. Saito M, et al. Self involution of giant keratoacanthoma on the tip of the nose. Plast Reconstr Surg 2003;111:1561—2. 35. Beare JM. Recurrent molluscum sebaceum. Lancet 1955;1: 182—3. 36. Silberberg I, Kopf A, Baer RL. Recurrent keratoacanthoma of the lip. Arch Dermatol 1962;86:44—53. 37. Rook A, Kerdel-Vegas F, Young JA. Las recidivas en el queratoacanthoma. Med Cutanea 1967;2:17—26. 38. Reymann F. Treatment of keratoacanthomas with curettage. Dermatologica 1977;155:90—6. 39. Epstein EH, Epstein EH. Keratoacanthoma recurrent after surgical excision. J Dermatol Surg Oncol 1978;4:524—5. 40. Habif TP. Extirpation of keratoacanthomas by blunt dissection. J Dermatol Surg Oncol 1980;6:652—4. 41. Larson PO. Keratoacanthomas treated with Mohs’ micrographic surgery (chemosurgery). J Am Acad Dermatol 1987; 16:1040—4. 42. Church RE. Molluscum pseudocarcinomatosum. Lancet 1955; 1:460—1. 43. Haws MJ, Neumeister MW, Kenneaster DG, Russell RC. Management of non-melanoma skin tumours of the hand. Clin Plast Surg 1997;24:779—95. 44. Griffiths RW, Feeley K, Suvarna SK. Audit of clinical and histological prognostic factors in primary invasive squamous cell carcinoma of the skin; assessment in a minimum 5 year follow-up study after conventional excisional surgery. Br J Plast Surg 2002;55:287—92. 45. Blessing K, Nafussi AAl, Gordon PM. The regressing keratoacanthoma. Histopathology 1994;24:381—4.
R.W. Griffiths
46. Bruner JM. Keratoacanthoma. Plast Reconstr Surg 1963;31: 281—8. 47. Brown FC, Tan EM. Immunological reaction in keratoacanthoma, a resolving skin tumor. Cancer Res 1973;33: 2030—3. 48. Patel A, Halliday GM, Cooke BE, StC Barnetson RS. Evidence that regression in keratoacanthoma is immunologically mediated: a comparison with squamous cell carcinoma. Br J Dermatol 1994;131:789—98. 49. Barnetson RS, Halliday GM. Regression in skin tumours: a common phenomenon. Aust J Dermatol 1997;38(Suppl): S63—5. 50. Flannery GR, Muller HK. Immune response to human keratoacanthoma. Br J Dermatol 1979;101:625—32. 51. Lowes MA, Bishop GA, Cooke BE, Barnetson RS, Halliday GM. Keratoacanthomas have an immunosuppressive cytokine environment of increased IL-10 and decreased GM-CSF compared to squamous cell carcinomas. Br J Cancer 1999; 80:1501—5. 52. Stevanovic DV. Recidivas du kerato-acanthome: reformation, exacerbation, recroissance, keratoacanthoma duplex. Ann de Dermatoloogie et de syphiligraphie 1969;96:415—20. 53. Beham A, Regauer S, Soyer H-P, Beham-Schmid C. Keratoacanthoma: a clinically distinct variant of well differentiated squamous cell carcinoma. Adv Anat Pathol 1998;5:269—80. 54. Canas GC, Robson KJ, Arpey CJ. Persistent keratoacanthoma: challenges in management. Dermatol Surg 1998;24:1364—9. 55. Finley AG. Keratoacanthoma. Aust J Dermatol 1954;2: 144—8. 56. Linell F, Mansson B. Molluscum pseudocarcinomatosum. Acta Radiol 1957;48:123—40. 57. Davies DG. Keratoacanthoma or squamous carcinoma ? J Laryngol Otol 1969;83:333—47. 58. Ghadially FN. A comparative morphological study of the keratoacanthoma of man and similar experimentally produced lesions in the rabbit. J Path Bact 1958;75:441—53. 59. Letzel S, Drexler H. Occupationally related tumours in tar refinery workers. J Am Acad Dermatol 1998;39:712—20. 60. 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:S35—8. 61. Barrett Brown J, Fryer MP. Fallacy of the term ‘self-healing epidermoid carcinoma’ and limitations of microscopic interpretations. Surg Gynecol Obstet 1955;100:179—83. 62. Wulsin JH. Keratoacanthoma: a benign cutaneous tumour arising in a skin graft donor site. Am Surg 1958;24:689—92. 63. Dibden FA, Fowler M. The multiple growth of molluscum sebaceum in donor and recipient sites of skin graft. Aust N Z J Surg 1958;25:157—9. 64. Hendricks WM. Sudden appearance of multiple keratoacanthomas three weeks after thermal burns. Cutis 1991;47: 410—2. 65. Hamilton SA, Dickson WA, O’Brien CJ. Keratoacanthoma developing in a split skin graft donor site. Br J Plast Surg 1997;50:560—4. 66. Tamir G, Morgenstern S, Ben-Amitay D, Okpn E, Hauben DJ. Synchronous appearance of keratoacanthomas in burn scar and skin graft donor site shortly after injury. J Am Acad Dermatol 1999;40:870—1. 67. Cox SE. Rapid development of keratoacanthomas after a body peel. Dermatol Surg 2003;29:201—3. 68. Jeremiah BS. Squamous cell carcinoma development on donor area following removal of a split thickness skin graft. Plast Reconstr Surg 1948;3:718—21. 69. Neilson D, Emerson DJM, Dunn L. Squamous cell carcinoma of
Keratoacanthoma observed
70.
71.
72.
73.
74.
75.
76.
77.
78.
79. 80.
81.
82.
83.
skin developing in a skin graft donor site. Br J Plast Surg 1988;41:417—9. Climo MS, Enos WF, King PG. Squamous cell carcinoma of the skin developing in a skin graft donor site. Br J Plast Surg 1989;42:118. Taylor CD, Snelling CFT, Nickerson D, Trotter MJ. Acute development of invasive squamous cell carcinoma in a split thickness skin graft donor site. J Burn Care Rehabil 1998;19: 382—5. Love RL, Breidahl AF. Acute squamous cell carcinoma arising within a recent burn scar in a 14 year old boy. Plast Reconstr Surg 2000;106:1069—71. Eidemiller LR, Fletcher WS, Dennis DL, Krippaehne WW. Spontaneous remission of proven cancer. Northwest Med 1971;70:539—43. Franchimont C, Pierard GE, Cauwenberge DV, Damseaux M, Lapiere ChM. Episodic progression and regression of basal cell carcinomas. Br J Dermatol 1982;106:305—10. Roseman JM. Regression of locally recurrent squamous cell carcinoma of the skin following excision of a metastasis: with a review of the literature. J Surg Oncol 1988;39:213—4. Royds JA, Stephenson TJ, Silcocks PB, Bleehan SS. Proliferating cell nuclear antigen immunostaining in keratoacanthoma and squamous cell carcinoma of the skin. Pathologica 1994;86:612—6. Prehn RT. The paradoxical association of regression with a poor prognosis in melanoma contrasted with a good prognosis in keratoacanthoma. Cancer Res 1996;56:937—40. Chang WYM. Complete spontaneous regression of cancer: four case reports, a review of the literature, and discussion of possible mechanisms involved. Hawaii Med J 2000;59: 379—87. Billingsley EM, Davis N, Helm KF. Rapidly growing squamous cell carcinoma. J Cut Med Surg 1999;3:193—7. Donaldson MJ, Sullivan TJ, Whitehead KJ, Williamson RM. Peri-ocular keratoacanthoma. Clinical features, pathology and management. Ophthalmology 2003;110:1403—7. Chalet MD, Connors RC, Ackerman AB. Squamous cell carcinoma vs. keratoacanthoma: criteria for histologic differentiation. J Dermatol Surg 1975;1:14—15. Waring AJ, Takata M, Rehman I, Rees JL. Loss of heterozygosity analysis of keratoacanthoma reveals multiple differences from cutaneous squamous cell carcinoma. Br J Cancer 1996;73:649—53. Binder M, Steiner A, Mossbacher U, Hunegnaw M, Peham-
501
84. 85.
86.
87.
88.
89.
90.
91.
92.
93. 94. 95. 96.
97.
berger H, Wolff K. Estimation of the volume-weighted mean nuclear volume discriminates keratoacanthoma from squamous cell carcinoma. Am J Dermatopathol 1998;20:453—8. Weedon D. Keratoacanthoma: a personal perspective. Curr Diag Pathol 2003;9:259—65. Ellis GL. Differentiating keratoacanthoma from squamous cell carcinoma of the lower lip: an analysis of intraepithelial elastic fibers and intracytoplasmic glycogen. Oral Surg 1983; 56:527—32. Hodak E, Jones RE, Ackerman AB. Solitary keratoacanthoma is a squamous cell carcinoma: three examples with metastases. Am J Dermatopathol 1993;15:332—42. Cribier B, Asch P-H, Grosshans E. Differentiating squamous cell carcinoma from keratoacanthoma using histological criteria. Dermatology 1999;199:208—12. Sanchez Yus ES, Simon P, Requena L, Ambrojo P, de Eusebio E. Solitary keratoacanthoma. A self healing proliferation that frequently becomes malignant. Am J Dermatopathol 2000;22:305—10. Clausen OPF, Beigi M, Bolund L, Kolvraa S, Gjersvik PJ, Mork G, de Angelis PM. Keratoacanthomas frequently show chromosomal aberrations as assessed by comparative genomic hybridisation. J Invest Dermatol 2002;119:1367—72. Biesterfield S, Josef J. Differential diagnosis of keratoacanthoma and squamous cell carcinoma of the epidermis by MIB-1 immunohistometry. AntiCancer Res 2002;22:3019—24. 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. Kim DK, Kim JY, Kim HT, Ham KH, Shon DG. A specific chromosome aberration in a keratoacanthoma. Cancer Genet Cytogenet 2003;142:70—2. LeBoit PE. Can we understand keratoacanthoma ? Am J Dermatopathol 2002;24:166—8. Butcher RB. Malignant potential of keratoacanthoma. Laryngoscope 1979;89:1092—8. Goette DK. Keratoacanthoma and its treatment. J Ass Milit Dermatol 1984;10:3—10. Kyrmizakis DE, Hajiioannou JK, Helidonis E. Giant keratoacanthoma of the lower lip. Otolaryngol Head Neck Surg 2003;128:904—5. Schwartz RA. Keratoacanthoma: a clinico-pathologic enigma. Dermatol Surg 2004;30:326—33.
Keratoacanthoma observedq Richard W. Griffiths Department of Plastic Surgery, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK Received 13 November 2003; accepted 1 May 2004
KEYWORDS Keratoacanthoma; Observation; Photographic record; Spontaneous involution
Summary Conventional advice for managing suspected keratoacanthoma is total excision because of concern that the lesion may be a squamous cell carcinoma and histological differentiation of the two lesions is difficult. Only isolated cases have been published where lesions have been observed, with photographic documentation, to spontaneous resolution. Over 11 years (1992 – 2002) the author made a primary clinical diagnosis of solitary keratoacanthoma in 19 patients based upon the history and lesion appearance. Two thigh skin graft donor site lesions, and one on the nose and one on the lower lip were excised when there was concern about their growth pattern. A fifth patient was not content to be observed and had the lesion curetted by an oncologist. The remaining 14 patients had observed lesions photographed sequentially until resolution. The commonest single site affected was the hand (five cases). The mean age was 65 years (42 – 86 years). The mean duration of the lesion at presentation was 9 weeks (4 –28 weeks), and the mean time to resolution from appearance was 27 weeks (12 –64 weeks). Mean follow-up after resolution was 3 years 5 months (range 9 months – 8 years). No recurrences occurred. No scar revisions were necessary. Claims that resolved keratoacanthomas leave poor quality scars that may need surgical revision, were not confirmed in this illustrated series which is the largest published to date. The principles of observational management are outlined and the natural history of the condition and patterns of spontaneous resolution described. Q 2004 Published by Elsevier Ltd on behalf of The British Association of Plastic Surgeons.
Although it is recognised that the condition called keratoacanthoma or molluscum sebaceum may regress spontaneously, 1,2 an overwhelming majority of authors advocate complete excision of the lesion, maintaining that either it may be an invasive squamous cell carcinoma, or that if left to involute it will leave a poor quality scar that may require surgical revision.3 – 21 In nearly 1000 pubq
This work was presented at the Summer Meeting of the British Association of Plastic Surgeons, Celtic Manor Hotel, Newport, Wales. Friday 4th July 2003. E-mail address: [email protected]
lished cases, only some 20% of lesions have been observed through to spontaneous regression,2,4,5,14, 16,22 – 34 and of all these putative keratoacanthomas, less than 2% (15 lesions) have been documented to regression with serial photographs16,22,24 – 27,29 – 34 (Table 1). Whilst there is only one report of keratoacanthoma recurring after spontaneous regression alone,35 it is established that the lesion can ‘recur’ after various types of surgical excision or other intervention during the phase of proliferation.24, 35 – 37,38 – 41 Such ‘recurrences’ occur swiftly within a few weeks and affect 3 – 8% of cases,17 and some
S0007-1226/$ - see front matter Q 2004 Published by Elsevier Ltd on behalf of The British Association of Plastic Surgeons. doi:10.1016/j.bjps.2004.05.007
486
R.W. Griffiths
Table 1 Published cases with serial photographs Author
Year
Fouracres and Whittick Calnan and Haber Thomson Peterkin et al. Rook and Champion Stranc and Robertson Wolinsky et al. Lucente Popkin Platt and Griffiths de Visscher et al. Saito et al.
1951 1955 1958 1962 1963 1979 1981 1985 1990 1995 1996 2003
Total
Lesions followed to resolution with sequential photography 1 1 1 1 1 3 1 1 1 2 1 1 15
authors have advocated that such ‘recurrences’ should lead to reclassification of the original lesion as squamous cell carcinoma.26,42,43 That such ‘recurrences’ are likely to represent a reactive process in the phase of proliferation rather than neoplastic change may be supported by the rarity of true local recurrence of invasive squamous cell carcinoma after complete excision.44 Because of the sparse documentation of the natural history and pattern of clinical regression in keratoacanthoma, the experience of one clinician was reviewed who had over more than 15 years maintained an observation policy for suspected keratoacanthoma, usually without prior biopsy, and with comprehensive follow-up. The patterns of proliferation and regression are described.
Materials and methods The author reviews his photographic records for all consecutive patients seen as outpatients with the clinical diagnosis of keratoacanthoma from 1992 to 2002, and the notes retrieved (this cohort did not include two previously reported cases32). Information was recorded of names, hospital numbers, dates of birth, date at presentation, length of history of the genesis of the lesions, and time to Table 2 Principles of management by observation Initial question—has the growth plateaued and is the lesion regressing No biopsy Close personal follow-up every 2 weeks Photograph at each attendance Be prepared to excise if patient and/or surgeon are concerned at growth pattern i.e. failure to regress
Figure 1 (A) Male age 48 years. Split thickness donor site thigh lesion present for 6 weeks. (B) Male age 69 years. Split thickness donor site thigh lesion present 11 weeks.
resolution and discharge from the follow up clinic. All photographic prints and transparencies were reviewed. Criteria for making a diagnosis of keratoacanthoma were a short history of a few weeks, and that the lesion had been larger, had reached a plateau and was now getting smaller, and the appearance of raised edges with a central keratin plug progressively fragmenting to leave a crater appearance, with or without hair growth in it. Biopsy was avoided (although some had been biopsied prior to referral) (Table 2). The clinical diagnosis of keratoacanthoma would not be entertained in the immuno-compromised patient, and in this group any new skin lesion would be excised. The management policy was to review patients
Keratoacanthoma observed
487
Figure 2 Male age 58 years. Initial lesion present 6 weeks nasal dorsum, then shown at 7 and 9 weeks, final view after excision and full thickness skin grafting.
every 2 weeks until resolution was confirmed, with photographs taken at each attendance. The same clinician saw all patients at all visits, with the exception of one patient who was seen sequentially by a consultant colleague and also seen by the author. Thus there was continuity with regard to recall for the last clinic appearance of the lesions, whether or not the immediately previous photograph was available. Patients were advised at the outset that if they preferred excision this would be
done, but they were warned that the scar quality could not be predicted. They were also counselled that ‘recurrence’ could occur if excision was performed in the phase of proliferation. Patients were advised that excision could be performed at any stage if they (or the surgeon) were unhappy about the pattern of resolution or growth, primarily lack of evidence of regression. If the ‘watch and wait policy’ was breached by some surgical intervention this was recorded.
Figure 3 Female age 57 years. Sequential views of lesion right lower lip, 5, 13 weeks after initial appearance, views after curettage and cautery 21 and 26 weeks after initial presentation.
488
Table 3 Excised lesions when observation curtailed Sex
Age prior treatment
Time of biopsy after lesion appeared (weeks)
Site
Hospital
Pathologist
Histological report
M M
48 None 69 None
None None
Thigh donor site Thigh donor site
X X
A B
M
58 Biopsy well differentiated squamous cell carcinoma
4 weeks
Nose
X
C
F
57 None
None
Lower lip
X
D
Invasive well differentiated squamous cell carcinoma Well differentiated squamous cell carcinoma considered but judged fully excised keratoacanthoma Squamo-proliferative lesion some features of keratoacanthoma but indistinguishable from invasive well differentiated squamous cell carcinoma Squamo-proliferative lesion, differentiation of keratoacanthoma from well differentiated squamous cell carcinoma cannot be made by histology alone
Table 4 Patient characteristics Growth pattern Previous intervention
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Regressing Proliferating Unsure Static Regressing Regressing Regressing Regressing Regressing Static Regressing Static Regressing Static
M M F M F M M M F M F M M M
83 42 61 66 51 52 57 75 86 70 50 74 72 80
No Paint spray Spectacles No No No Paraffin/work No No No No No Pinched on metal Rotivator injury
History (weeks) Site
No 8 Curette/cautery at 5/7 weeks 7 No 7 No 6 Biopsy at 4 weeks 11 No 28 No 8 Biopsy at 2 weeks 12 No 6 No 8 No 6 No 4 Biopsy 5 weeks 8 No 8
Cheek Nose Nose Lower lip R hand R hand R hand Eyebrow Upper lip Cheek Alar base Nose R hand R ring finger
Time to resolution (weeks) Follow-up years/months 16 19 15 16 31 48 28 64 26 16 32 12 23 24
6 year 9 months 8 year 6 year 10 months 4 year 10 months 4 year 3 year 10 months 3 year 8 months 2 year 7 months 2 year 2 months 2 year 4 months 1 year 7 months 1 year 1 months 9 months 11 months
R.W. Griffiths
Number Sex Age (years) Previous trauma
Keratoacanthoma observed
489
Figure 4 Male age 75 years. Right eyebrow lesion biopsied (prior to referral) 2 weeks after first appearance, views 12, 21, 39 and 64 weeks after initial appearance.
Patients and their general medical practitioners were contacted during 2003 to determine if the lesion had recurred after discharge from clinic follow-up. Scar quality was assessed by visual inspection by patient and surgeon. Patients’ written consent was obtained to use their photographs as illustrations, and for the one patient who died (of unrelated cause) nearly 7 years after lesion resolution his wife’s written consent to use the photographs was obtained. Table 5 Anatomical sites of lesions Site of lesions
14 Patients
Right hand Nose Cheek Lower lip Upper lip Eyebrow
5 4 2 1 1 1
Results Over the 11 year period the author made a confident primary clinical diagnosis of keratoacanthoma in 19 patients based upon the history and lesion appearance. Two thigh skin graft donor site lesions (Fig. 1(A) and (B)), and one on the nose (Fig. 2) and one on the lower lip (Fig. 3) were excised when there was subsequent concern about their growth pattern and specifically lack of sustained regression. The histological reports for these four lesions are given (Table 3). A fifth patient elected to have the lesion curetted by an oncologist. The remaining 14 patients had observed lesions photographed sequentially until resolution (Figs. 4 – 17). The quality of resultant scars after spontaneous regression is well illustrated for the various anatomical sites. A summary of comparative patient data is given (Table 4). Eight patients gave
490
R.W. Griffiths
Figure 5
Female age 86 years. Upper lip lesion views 6, 10, 14 and 29 weeks after initial appearance.
a history of the lesion getting smaller, four indicated growth had stopped, one lesion was proliferating (patient 2, Fig. 12) and one patient was not sure about the growth pattern. Male:female ratio was 10:4. Fourteen of the patients were referred from dermatologists. The commonest single affected site was the hand (five cases), (Table 5). Possible irritation from chemical or mechanical trauma was recorded for five patients with 3/5 having lesions on the hand. The mean duration of the lesion at presentation was 9 weeks (4 – 28 weeks), the mean age was 65 years (42 – 86 years) and the mean time to resolution from appearance was 27 weeks (12 – 64 weeks). The patient observed to 64 weeks was advised in writing at 20 weeks that the surgeon considered lesion excision appropriate when he felt resolution was too slow but the patient declined. This patient subsequently had longer intervals between visits and was seen on nine occasions over the observation period. Only four patients had a biopsy or curettage elsewhere before referral, all others were simply observed. The histological findings for these are given in Table 6. The times to resolution for those
biopsied were 19, 23, 31 and 64 weeks (mean 34 weeks). For those not biopsied the resolution time ranged 12 – 48 weeks (mean 23 weeks). Patients tolerated follow-up well once they saw the lesion getting smaller. Mean follow-up after regression was 3 years 5 months (range 9 months –8 years), with only two patients having less than 1 year of follow-up — 9 and 11 months, respectively. No recurrences have occurred. No scars were revised surgically and all scars were acceptable to the patients.
Discussion Since the widespread recognition of keratoacanthoma as a clinical entity some 50 years ago,23 there has been a vigorous debate about the advisability and desirability of observing lesions clinically diagnosed as keratoacanthoma. The diagnosis can be made on the short history, with a plateau of growth, and usually some definite resolution/involution noted by the patient, coupled with the appearance of the lesion which may contain hair,32 and a central keratin plug and signs
Keratoacanthoma observed
Figure 6 Male age 66 years. Lower lip lesion views 6, 8, 10 and 17 weeks after initial appearance.
Figure 7 Male age 83 years. Right cheek lesion views 12 and 20 weeks after initial appearance.
491
492
Figure 8 Male age 70 years. Right cheek/eyelid lesion views 8, 11 and 16 weeks after initial appearance.
of fragmentation and generally an appearance unlike that of a typical squamous cell carcinoma. The experience of the clinician is crucial. In this series, eight lesions had a clear history of regression, and four had stopped growing and had reached a plateau. That keratoacanthomas can spontaneously regress is well recognised,1,2,25,26,29,32,45 with Musso1 noting that after a one third biopsy there could be further growth before regression. Bruner,46 however, counselled against biopsy as being misleading and advocated excising the whole lesion. Rook and Champion27 reported that excision Table 6 Prior biopsy for observed lesions Sex
Age
Prior treatment
Time of biopsy after lesion appeared (weeks)
Site
Hospital
Pathologist
Histological report
M
42
Curette/cautery biopsy
Nose
F
51
Biopsy
5 weeks 7 weeks 4 weeks
Hand
Y Y Y
E F E
M
75
Biopsy
2 weeks
Eyebrow
Z
G
M
72
Biopsy
5 weeks
Hand
Z
H
Keratoacanthoma incompletely excised Well differentiated squamous cell carcinoma Squamo-proliferative hyper-keratotic lesion—insufficient for assessment for either keratoacanthoma or well differentiated squamous cell carcinoma Keratoacanthoma and squamous cell carcinoma cannot be distinguished reliably on this material Squamo-proliferative lesion cannot be distinguished between pseudo-carcinoma and neoplasia including well differentiated squamous cell carcinoma and keratoacanthoma
R.W. Griffiths
Keratoacanthoma observed
Figure 9
493
Female age 50 years. Left alar base lesion, views 6, 15 and 33 weeks after initial appearance.
of the lesion in the growth phase can be followed by ‘recurrence’ although more accurately this could be described as continuing growth prior to involution. Whilst some authors consider this regression to have an immunological basis,47 – 49 others have failed to demonstrate an immune effect.50,51 Keratoacanthoma can continue to regrow or ‘recur’ after various interventions, including Mohs’ surgery.14,27,35,36,38 – 41,52, and this may be more likely if ablation of the lesion has been incomplete such as with curettage (Fig. 12).The rates of recurrence have been given as 3 – 8%.17,37,53 Occasionally such ‘recurrences’ may be protracted and resistant to multi-modal treatment.54 Such ‘recurrences’ are evident within a few weeks of biopsy or other intervention such as curettage and probably represent a recrudescence of the phase of proliferation which the initial treatment did not abort.37 This is dramatically shown in Fig. 12 from the present series where there was continued growth for 20 – 30 days after two episodes of curettage and biopsy elsewhere prior to regression starting. If, however, such ‘recurrences’ occur months later then it will be wise to question the initial diagnosis, and consider if the lesion was a squamous cell carcinoma.42,43 Further reassurance should be drawn from the observation that local recurrence of invasive squamous cell carcinoma after conventional complete excision surgically and histologically is extremely rare and when recurrence does occur in some 7% it is as regional lymph node metastases.44 Only a single case report of ‘recurrence’ has been identified when spontaneous resolution has been just that, with neither prior biopsy or any other form of intervention.35 Several authors have advocated excision of keratoacanthomas claiming that spontaneous regression in their experience produces poor quality scars.4,19,26,55 – 57 Several of these authors also reasonably argue that the
patient should not have to tolerate the lesion over the course of its natural history to regression. In the present series though a majority of the cases illustrated if excised, could well have required skin grafting (including the hand lesions), and in other cases in more cosmetically sensitive areas (Figs. 8, 11 and 12) it could be persuasively argued that surgical excision and repair would have given a poorer result than that observed after spontaneous regression. Patients were generally very tolerant of the observation policy once they knew the likely consequences of surgical excision. It would be reasonable, however, to question the necessity for follow-up, as frequently as every 2 weeks, and from the experience of this study in which no lesions observed to resolution recurred, then follow-up every 4 weeks if there is evidence of sustained regression may well be adequate. The longer the follow-up interval the greater the need to impress upon the patient, the need to return immediately if the lesion enlarges. If the conservative approach is adopted it must be followed with a degree of circumspection as emphasised by Jackson8, in case the clinical diagnosis is in error and the lesion represents an enlarging squamous cell carcinoma. The principles of management must include a single senior clinician observing the patient from presentation to lesion resolution, and the lesion photographed every 2 –3 weeks. The key point in the history is a lesion diminishing in size or at least one that has stopped enlarging. The patient must be advised of the likely time scale to resolution (over 6 months on average as we have found), and also understand that at any time, if they wish, the lesion can be excised, but that the price of such surgical intervention may be an inferior cosmetic result. Advice on the possibility of ‘recurrence’ if excised in the phase of proliferation must also be given. The
494
R.W. Griffiths
Figure 10 Female age 61 years. Nasal dorsum lesion, views 7, 12, 13 and 16 weeks after initial appearance.
Keratoacanthoma observed
Figure 11
Male age 74 years. Nasal dorsum lesion views 4, 6, 10 and 13 weeks after initial appearance.
495
496
R.W. Griffiths
Figure 12 Male age 42 years. Left alar lesion, biopsied and curetted (prior to referral) 5 weeks after initial appearance; views 7, 9, 11, 19 and 32 weeks after initial appearance.
patient must clearly acknowledge that defaulting from follow-up is not an option. In the present series, there were no local recurrences or node metastases observed in the mean follow-up period of 3 years 5 months, with only two patients at present having less than 12 months follow up (11 and 9 months). The aetiology of keratoacanthoma is unclear. It can be induced experimentally in rabbits,58 and it has been described in humans to follow after 29 years of chronic irritation in the tar industry.59 Haws et al.43 described 11 –16% of keratoacanthomas to occur on the hand. With the single largest number of lesions in our series occurring on the hand, trauma may be important in some cases,60 as with its description in relation to healing skin graft donor sites and burns61 – 66 and after chemical skin
peeling. 67 It maybe that some of the acute squamous cell carcinomas described in skin graft donor sites and burn scars are in fact keratoacanthomas.68 – 72 If keratoacanthomas in fact represent well differentiated squamous cell carcinomas which spontaneously regress, then this behaviour may illustrate one end of the spectrum of behaviour of neoplasia within which spontaneous regression of malignancy is well described.49,73 – 78 Where there is real doubt regarding the clinical differentiation of keratoacanthoma from rapidly growing squamous cell carcinoma, excision is advocated.79,80 I believe this particularly holds true for skin lesions arising in immuno-compromised patients and I would not be prepared to observe lesions in
Figure 13 Male age 52 years. Right hand dorsum lesion, views 24, 29 and 35 weeks after initial appearance.
Keratoacanthoma observed
497
Figure 14 Female age 51 years. Right hand dorsum lesion, biopsied (prior to referral) 4 weeks after initial appearance, views 11, 14, 22 and 31 weeks after initial appearance.
Figure 15 Male age 72 years. Right hand dorsum lesion, views 10, 12, 23 and 30 weeks after initial appearance.
498
R.W. Griffiths
Figure 16 Male age 57 years. Right hand dorsum/base middle finger lesion, views 8, 11, 13 and 31 weeks after initial appearance.
these patients. Also if a patient is judged likely to be noncompliant with the strict follow-up regime, then it will be wiser to excise any suspicious lesions. The histological differentiation of keratoacanthoma from invasive squamous cell carcinoma is not easy, and this is clearly demonstrated in the histopathology reports from eight separate pathologists in three different hospitals given in Tables 3 and 6. Whilst some authors consider the histological and cytological differentiation precise, sure and possible,48,81 – 84 others regard the two conditions as representing a range of neoplastic activity with no clear distinction.6,8,9,11,13,85 – 88 The differential diagnosis of the two conditions is difficult not only with conventional histology,49 but also with more sophisticated techniques,89 – 91 although in one recent case of keratoacanthoma a specific chromosome aberration has been described.92 If there is medico-legal concern about observation of presumptive keratoacanthomas, after biopsy fails to exclude squamous cell carcinoma, then this must be set against the genuine histological difficulties of differentiating the two lesions after which close clinical observation becomes one legitimate option for management. LeBoit93 has written ‘no one has done a double-blind study, in
which keratoacanthoma either diagnosed by clinical appearance or by partial biopsy, have been allowed to play out their life histories’, and suggested the topic as a wonderful research opportunity ‘for young energetic dermatopathologists who bemoan the fact that the ‘old guys’ got all the good stuff, here is something to keep you occupied. Figure out the mechanism by which keratoacanthoma regresses, and see if it can be applied to other neoplasms. There might be a trip to Stockholm in it!’ Cribier et al.87 in consideration of 296 cases wrote ‘many of the criteria commonly used for the differential diagnosis of squamous cell carcinoma and keratoacanthoma are not reliable. The combination of the five most useful criteria does not significantly increase the specificity or sensitivity of the histological diagnosis in difficult cases. Atypical or difficult cases should, therefore, be considered and treated as squamous cell carcinoma since a clear cut distinction is not possible even with the aid of the most relevant criteria’. There are other treatments for keratoacanthoma, apart from surgical excision—curettage, cryotherapy, electrodessication, irradiation, 5 FU and steroids,94 – 96 but the efficacy of these therapies
Keratoacanthoma observed
499
warned of this possibility—and the surgeon not surprised when this sometimes happens. It may be that Schwartz’s concept is helpful when he concluded that keratoacanthoma is an abortive malignancy that rarely progresses into invasive squamous cell carcinoma.97
Acknowledgements I am very pleased to thank my colleague David Dujon for agreement to report on one patient with the lesion of the finger (Fig. 17). I am also most grateful to Robert Salthouse for his skill in producing the various illustrations for this paper.
References
Figure 17 Male age 80 years. Right index finger lesion, views 8, 12 and 24 weeks after initial appearance.
will of course remain unclear if used on lesions which the present study has demonstrated are consistently capable of spontaneous regression. The present series did not rely on histopathological interpretation and represents a precise clinical study of the behaviour of lesions clinically diagnosed as keratoacanthoma. Whilst for convenience of patient and surgeon the decision may be frequently taken to excise such lesions early, this should be done in the full knowledge that if some of these are treated in the phase of proliferation they may continue to grow, and patients should be
1. Musso L. Spontaneous resolution of molluscum sebaceum. Br J Dermatol 1951;63:151—3. 2. Rook A, Whimster I. Le kerato-acanthome. Arch Belges Dermatol Syph 1950;6:137—46. 3. Hutchinson J. Morbid growths and tumours 1. The crateriform ulcer of the face, a form of acute epithelial cancer. Trans Path Soc 1889;40:275—81. 4. Beare JM. Molluscum sebaceum. Br J Surg 1953;41:167—72. 5. Hueston JT. Molluscum sebaceum. Aust N Z J Surg 1956;26: 25—31. 6. Middleton AG, Curtin JW. Keratoacanthoma or squamous cell carcinoma. A surgeon’s dilemma. Plast Reconstr Surg 1966; 38:56—63. 7. Garrett WS, Ware JL, Thorne FL. Keratoacanthoma. Arch Surg 1967;94:853—7. 8. Jackson IT. Diagnostic problem of keratoacanthoma. Lancet 1969;1:490—2. 9. Neuman Z, Giladi A. Plea for a radical approach in so-called keratoacanthoma of the eyelid. Plast Reconstr Surg 1971; 47:231—3. 10. Cohen N, Plaschkes Y, Pevzner S, Loewenthal M. Review of 57 cases of keratoacanthoma. Plast Reconstr Surg 1972;49: 138—42. 11. Iverson RE, Vistnes LM. Keratoacanthoma is frequently a dangerous diagnosis. Am J Surg 1973;126:359—65. 12. Schnur PL, Bozzo P. Metastasising keratoacanthomas ? Plast Reconstr Surg 1978;62:258—62. 13. Sanders GH, Miller TA. Are keratoacanthomas really squamous cell carcinomas ? Ann Plast Surg 1982;9:306—9. 14. Kingman J, Callen JP. Keratoacanthoma. Arch Dermatol 1984;120:736—40. 15. Stal S. Keratoacanthoma. Clin Plast Surg 1987;14:423. 16. Popkin GL. Tumors of the skin: a dermatologist’s viewpoint. In: Mc Carthy JG, editor. Plastic surgery. Tumors of the head and neck and skin, vol. 5. Philadelphia: WB Saunders; 1990; p. 3560—613. 17. Goslen JB. Chapter 55, Management of keratoacanthomas, in Wheeland RG ed, Cutaneous Surgery. Philadelphia: WB Saunders; 1994, p. 723—30. 18. Schwartz RA. Keratoacanthoma. J Am Acad Dermatol 1994; 30:1—19. 19. Burns T. Recognising and managing keratoacanthoma. Practitioner 1997;241:424.
500
20. Manstein CH, Frauenhoffer CJ, Besden JE. Keratoacanthoma: is it a real entity ? Ann Plast Surg 1998;40: 469—72. 21. Ghadially R, Ghadially FN. Chapter 82, Keratoacanthoma, in Freedberg IM, et al., editors. Fitzpatrick’s dermatology in general medicine 5th edn. New York: McGraw Hill; 1999, p. 865—72. 22. Fouracres FA, Whittick JW. The relationship of molluscum sebaceum (keratoacanthoma) to spontaneous healing epithelioma of the skin. Br J Cancer 1953;7:58—64. 23. Levy EJ, Shaffer B, Beerman H. Keratoacanthoma. JAMA 1954;155:562—4. 24. Calnan CD, Haber H. Molluscum sebaceum. J Path Bact 1955; 69:61—6. 25. Thomson S. Molluscum sebaceum and its surgical signficance. Ann Roy Coll Surg Engl 1958;22:382—400. 26. Peterkin GAG, MacMillan JB, MacLean S. Pseudo-carcinoma of the skin. A follow up of cases of keratoacanthoma seen in the 10 years 1951—1960. Scot Med J 1962;7:27—35. 27. Rook A, Champion RH. Keratoacanthoma. NCI Monographs 1963;10:257—73. 28. Rank BK, Dixon PL. Another look at keratoacanthoma. Aust N Z J Surg 1979;49:654—8. 29. Stranc MF, Robertson GA. Conservative treatment of keratoacanthomas. Ann Plast Surg 1979;2:525—30. 30. Wolinsky S, Silvers DN, Kohn SR, Sanders SL, Herman EW. Spontaneous regression of a giant keratoacanthoma. Photographic documentation and histopathologic correlation. J Dermatol Surg Oncol 1981;7:897—901. 31. Lucente FE. Giant keratoacanthoma of the nose. Otolaryngol Head Neck Surg 1985;93:112—6. 32. Platt AJ, Griffiths RW. Keratoacanthoma: the value of photographic follow-up in conservative management. Eur J Plast Surg 1995;18:85—7. 33. De Visscher JGAM, van der Wal JE, Starink ThM, Tiwari RM, van der Wal I. Giant keratoacanthoma of the lower lip. Report of a case of spontaneous regression. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:193—6. 34. Saito M, et al. Self involution of giant keratoacanthoma on the tip of the nose. Plast Reconstr Surg 2003;111:1561—2. 35. Beare JM. Recurrent molluscum sebaceum. Lancet 1955;1: 182—3. 36. Silberberg I, Kopf A, Baer RL. Recurrent keratoacanthoma of the lip. Arch Dermatol 1962;86:44—53. 37. Rook A, Kerdel-Vegas F, Young JA. Las recidivas en el queratoacanthoma. Med Cutanea 1967;2:17—26. 38. Reymann F. Treatment of keratoacanthomas with curettage. Dermatologica 1977;155:90—6. 39. Epstein EH, Epstein EH. Keratoacanthoma recurrent after surgical excision. J Dermatol Surg Oncol 1978;4:524—5. 40. Habif TP. Extirpation of keratoacanthomas by blunt dissection. J Dermatol Surg Oncol 1980;6:652—4. 41. Larson PO. Keratoacanthomas treated with Mohs’ micrographic surgery (chemosurgery). J Am Acad Dermatol 1987; 16:1040—4. 42. Church RE. Molluscum pseudocarcinomatosum. Lancet 1955; 1:460—1. 43. Haws MJ, Neumeister MW, Kenneaster DG, Russell RC. Management of non-melanoma skin tumours of the hand. Clin Plast Surg 1997;24:779—95. 44. Griffiths RW, Feeley K, Suvarna SK. Audit of clinical and histological prognostic factors in primary invasive squamous cell carcinoma of the skin; assessment in a minimum 5 year follow-up study after conventional excisional surgery. Br J Plast Surg 2002;55:287—92. 45. Blessing K, Nafussi AAl, Gordon PM. The regressing keratoacanthoma. Histopathology 1994;24:381—4.
R.W. Griffiths
46. Bruner JM. Keratoacanthoma. Plast Reconstr Surg 1963;31: 281—8. 47. Brown FC, Tan EM. Immunological reaction in keratoacanthoma, a resolving skin tumor. Cancer Res 1973;33: 2030—3. 48. Patel A, Halliday GM, Cooke BE, StC Barnetson RS. Evidence that regression in keratoacanthoma is immunologically mediated: a comparison with squamous cell carcinoma. Br J Dermatol 1994;131:789—98. 49. Barnetson RS, Halliday GM. Regression in skin tumours: a common phenomenon. Aust J Dermatol 1997;38(Suppl): S63—5. 50. Flannery GR, Muller HK. Immune response to human keratoacanthoma. Br J Dermatol 1979;101:625—32. 51. Lowes MA, Bishop GA, Cooke BE, Barnetson RS, Halliday GM. Keratoacanthomas have an immunosuppressive cytokine environment of increased IL-10 and decreased GM-CSF compared to squamous cell carcinomas. Br J Cancer 1999; 80:1501—5. 52. Stevanovic DV. Recidivas du kerato-acanthome: reformation, exacerbation, recroissance, keratoacanthoma duplex. Ann de Dermatoloogie et de syphiligraphie 1969;96:415—20. 53. Beham A, Regauer S, Soyer H-P, Beham-Schmid C. Keratoacanthoma: a clinically distinct variant of well differentiated squamous cell carcinoma. Adv Anat Pathol 1998;5:269—80. 54. Canas GC, Robson KJ, Arpey CJ. Persistent keratoacanthoma: challenges in management. Dermatol Surg 1998;24:1364—9. 55. Finley AG. Keratoacanthoma. Aust J Dermatol 1954;2: 144—8. 56. Linell F, Mansson B. Molluscum pseudocarcinomatosum. Acta Radiol 1957;48:123—40. 57. Davies DG. Keratoacanthoma or squamous carcinoma ? J Laryngol Otol 1969;83:333—47. 58. Ghadially FN. A comparative morphological study of the keratoacanthoma of man and similar experimentally produced lesions in the rabbit. J Path Bact 1958;75:441—53. 59. Letzel S, Drexler H. Occupationally related tumours in tar refinery workers. J Am Acad Dermatol 1998;39:712—20. 60. 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:S35—8. 61. Barrett Brown J, Fryer MP. Fallacy of the term ‘self-healing epidermoid carcinoma’ and limitations of microscopic interpretations. Surg Gynecol Obstet 1955;100:179—83. 62. Wulsin JH. Keratoacanthoma: a benign cutaneous tumour arising in a skin graft donor site. Am Surg 1958;24:689—92. 63. Dibden FA, Fowler M. The multiple growth of molluscum sebaceum in donor and recipient sites of skin graft. Aust N Z J Surg 1958;25:157—9. 64. Hendricks WM. Sudden appearance of multiple keratoacanthomas three weeks after thermal burns. Cutis 1991;47: 410—2. 65. Hamilton SA, Dickson WA, O’Brien CJ. Keratoacanthoma developing in a split skin graft donor site. Br J Plast Surg 1997;50:560—4. 66. Tamir G, Morgenstern S, Ben-Amitay D, Okpn E, Hauben DJ. Synchronous appearance of keratoacanthomas in burn scar and skin graft donor site shortly after injury. J Am Acad Dermatol 1999;40:870—1. 67. Cox SE. Rapid development of keratoacanthomas after a body peel. Dermatol Surg 2003;29:201—3. 68. Jeremiah BS. Squamous cell carcinoma development on donor area following removal of a split thickness skin graft. Plast Reconstr Surg 1948;3:718—21. 69. Neilson D, Emerson DJM, Dunn L. Squamous cell carcinoma of
Keratoacanthoma observed
70.
71.
72.
73.
74.
75.
76.
77.
78.
79. 80.
81.
82.
83.
skin developing in a skin graft donor site. Br J Plast Surg 1988;41:417—9. Climo MS, Enos WF, King PG. Squamous cell carcinoma of the skin developing in a skin graft donor site. Br J Plast Surg 1989;42:118. Taylor CD, Snelling CFT, Nickerson D, Trotter MJ. Acute development of invasive squamous cell carcinoma in a split thickness skin graft donor site. J Burn Care Rehabil 1998;19: 382—5. Love RL, Breidahl AF. Acute squamous cell carcinoma arising within a recent burn scar in a 14 year old boy. Plast Reconstr Surg 2000;106:1069—71. Eidemiller LR, Fletcher WS, Dennis DL, Krippaehne WW. Spontaneous remission of proven cancer. Northwest Med 1971;70:539—43. Franchimont C, Pierard GE, Cauwenberge DV, Damseaux M, Lapiere ChM. Episodic progression and regression of basal cell carcinomas. Br J Dermatol 1982;106:305—10. Roseman JM. Regression of locally recurrent squamous cell carcinoma of the skin following excision of a metastasis: with a review of the literature. J Surg Oncol 1988;39:213—4. Royds JA, Stephenson TJ, Silcocks PB, Bleehan SS. Proliferating cell nuclear antigen immunostaining in keratoacanthoma and squamous cell carcinoma of the skin. Pathologica 1994;86:612—6. Prehn RT. The paradoxical association of regression with a poor prognosis in melanoma contrasted with a good prognosis in keratoacanthoma. Cancer Res 1996;56:937—40. Chang WYM. Complete spontaneous regression of cancer: four case reports, a review of the literature, and discussion of possible mechanisms involved. Hawaii Med J 2000;59: 379—87. Billingsley EM, Davis N, Helm KF. Rapidly growing squamous cell carcinoma. J Cut Med Surg 1999;3:193—7. Donaldson MJ, Sullivan TJ, Whitehead KJ, Williamson RM. Peri-ocular keratoacanthoma. Clinical features, pathology and management. Ophthalmology 2003;110:1403—7. Chalet MD, Connors RC, Ackerman AB. Squamous cell carcinoma vs. keratoacanthoma: criteria for histologic differentiation. J Dermatol Surg 1975;1:14—15. Waring AJ, Takata M, Rehman I, Rees JL. Loss of heterozygosity analysis of keratoacanthoma reveals multiple differences from cutaneous squamous cell carcinoma. Br J Cancer 1996;73:649—53. Binder M, Steiner A, Mossbacher U, Hunegnaw M, Peham-
501
84. 85.
86.
87.
88.
89.
90.
91.
92.
93. 94. 95. 96.
97.
berger H, Wolff K. Estimation of the volume-weighted mean nuclear volume discriminates keratoacanthoma from squamous cell carcinoma. Am J Dermatopathol 1998;20:453—8. Weedon D. Keratoacanthoma: a personal perspective. Curr Diag Pathol 2003;9:259—65. Ellis GL. Differentiating keratoacanthoma from squamous cell carcinoma of the lower lip: an analysis of intraepithelial elastic fibers and intracytoplasmic glycogen. Oral Surg 1983; 56:527—32. Hodak E, Jones RE, Ackerman AB. Solitary keratoacanthoma is a squamous cell carcinoma: three examples with metastases. Am J Dermatopathol 1993;15:332—42. Cribier B, Asch P-H, Grosshans E. Differentiating squamous cell carcinoma from keratoacanthoma using histological criteria. Dermatology 1999;199:208—12. Sanchez Yus ES, Simon P, Requena L, Ambrojo P, de Eusebio E. Solitary keratoacanthoma. A self healing proliferation that frequently becomes malignant. Am J Dermatopathol 2000;22:305—10. Clausen OPF, Beigi M, Bolund L, Kolvraa S, Gjersvik PJ, Mork G, de Angelis PM. Keratoacanthomas frequently show chromosomal aberrations as assessed by comparative genomic hybridisation. J Invest Dermatol 2002;119:1367—72. Biesterfield S, Josef J. Differential diagnosis of keratoacanthoma and squamous cell carcinoma of the epidermis by MIB-1 immunohistometry. AntiCancer Res 2002;22:3019—24. 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. Kim DK, Kim JY, Kim HT, Ham KH, Shon DG. A specific chromosome aberration in a keratoacanthoma. Cancer Genet Cytogenet 2003;142:70—2. LeBoit PE. Can we understand keratoacanthoma ? Am J Dermatopathol 2002;24:166—8. Butcher RB. Malignant potential of keratoacanthoma. Laryngoscope 1979;89:1092—8. Goette DK. Keratoacanthoma and its treatment. J Ass Milit Dermatol 1984;10:3—10. Kyrmizakis DE, Hajiioannou JK, Helidonis E. Giant keratoacanthoma of the lower lip. Otolaryngol Head Neck Surg 2003;128:904—5. Schwartz RA. Keratoacanthoma: a clinico-pathologic enigma. Dermatol Surg 2004;30:326—33.