Keywords
keratoacanthoma - koebnerization - full-thickness skin graft
Introduction
The term, keratoacanthoma (KA) was first coined in the 1940s.[1] KA are historically considered to be a variant of squamous cell carcinoma (SCC);
however, it has been suggested to be defined as a benign tumor due to the numerous
cases of spontaneous regression.[2] Despite the controversy, KA remains classified as a variant of SCC in the 2018 World
Health Organization classification.[3] KA typically presents as a rapidly growing dome-shaped umbilicated nodule with a
central hyperkeratotic plug,[4] undergoing three stages: proliferative, mature, and regression phase.[2] The similarity of the triphasic nature of KA to the follicular morphogenesis of
anagen, catagen, and telogen cycles, suggests that KA has a follicular origin and
may be associated with Wnt signaling.[2] Representative KA types include solitary, centrifugum et marginatum, and giant.[2] Excluding solitary KA, all other types are reportedly associated with human papilloma
virus (HPV) infection.[2]
In addition to the SCC-associated risk factors, trauma, including surgery, is also
a potential risk factor for KA.[2]
[4] There are few reports on trauma after skin grafting. If KA occurs after skin grafting,
it may be misdiagnosed as SCC without consultation with a dermatologist, which in
turn can lead to invasive treatment such as wide excision. This report highlights
a case of KA that occurred at the recipient site of full-thickness skin graft (FTSG),
which has educational value.
Case
A 57-year-old Korean man without any contributory medical history visited the dermatology
department with a solitary pigmented papule, 0.4 cm in diameter, on the left lower
eyelid ([Fig. 1A]). Skin biopsy revealed a basal cell carcinoma (BCC) with peripheral palisading and
peritumoral cleft ([Fig. 1B]). After wide excision, FTSG from left preauricular area was used for reconstruction
during plastic surgery ([Fig. 1C]).
Fig. 1 Clinical and histopathological features of preceding skin lesion. (A) Solitary rodent-ulcer like pigmented papule on the left lower eyelid. (B) Histopathological specimen was compatible with basal cell carcinoma, showing numerous
nests of basaloid tumors with peripheral palisading and peritumoral cleft. (C-1) Preoperative design on the left lower eyelid. (C-2) Photograph immediately after tumor removal. (C-3) Preauricular donor site. (C-4) Photograph immediately after skin graft.
Two weeks postoperatively, an erythematous nodule developed in the lower margin of
the skin graft recipient site. The nodule rapidly attained a dome shape with a central
hyperkeratotic plug over the following 2 weeks ([Fig. 2A]). During dermatologic consultation, the patient was diagnosed with KA, and a surgical
excision with 3 mm margin was performed ([Fig. 2B]). Histopathological findings revealed a large, well-differentiated, squamous tumor
with central keratin-filled crater ([Fig. 2C]). A buttress of normal epidermis surrounded the crater. Keratin horn pearls, bland
squamous cells with abundant eosinophilic or glassy cytoplasm with minimal atypia,
were also observed. The tissue tested negative for HPV genotyping. The remaining defect
was closed with a split-thickness skin graft harvested from the left lateral thigh
([Fig. 2D]). No signs of recurrence were observed 3 months postoperatively.
Fig. 2 Clinical and histopathological features of keratoacanthoma (KA). (A) Solitary dome-shaped nodule with central keratotic plug on the left lower eyelid.
(B) The center of nodule located on the lower margin of skin graft (red arrow head).
(C) Large, well-differentiated squamous tumor with central keratin-filled crater, consistent
with KA. (D) Excision with split-thickness skin graft was performed.
Discussion
KA classically presents as a firm, dome-shaped nodule filled with a keratinous plug.[2]
[4] It has been associated with old age, HPV infection, immunosuppression, ultraviolet
(UV) exposure, and cutaneous traumas such as surgery, laser resurfacing, and burns.[2] The patient in the present case tested negative for HPV deoxyribonucleic acid on
polymerase chain reaction analysis. Considering his age and medical history, it is
unlikely that the patient was immunosuppressed. [Table 1] summarizes the reported cases of KA after skin grafting according to the patient
demographic and case data. The occurrence of KA at the skin graft site is rare, and
in most of the 11 reported cases, the KA developed at the donor site.[5]
[6]
[7] Moreover, the cases that report KA development on the recipient site are recurrences
of multiple KAs in the extremities of older patients.[5]
[9]
[11]
[10] The mechanism of KA formation after receiving a skin graft is unclear due to its
multifactorial etiology.[10] A two-step pathogenesis, characterized by two triggering insults to the epidermis,
has been proposed.[6]
[7]
[11] The first insult (initiator) may be oncogenic UV exposure of the epidermis or the
mutation of cell-cycle regulators due from a chemical carcinogen. The KA in our patient
also occurred in a sun-exposed area (lower eyelid) where BCC had previously presented.
We believe that a potential first insult may have been a mutation in the cell-cycle
regulator due to UV exposure. The trauma associated with surgery may have been the
second insult (promoter) to induce epithelial proliferation. The local upregulation
of cytokines and chemokines from recruitment of neutrophil, macrophage, and T cells
may be involved in the acute wound healing process.[11] Helper T cells enhance skin carcinogenesis.[12] Fibroblast growth factor is involved in the Koebner phenomenon of psoriasis,[13] characterized by the appearance of skin lesions following trauma in a previously
affected site. Therefore, epithelial proliferation and angiogenesis may be induced
by these cells after acute epidermal injury.[11] Contrastingly, cytotoxic T cells are involved in KA regression. After skin grafting,
microscarring reduces lymphatic regeneration, thereby decreasing local immunosurveillance;
this factor places higher risk among older patients with immunosenescence.[11] In a previously reported case of recurrent multiple KA in older patients, local
and systemic immunosuppression were presumably involved. Considering these findings
and reports, the two-step pathogenesis presents an acceptable explanation for the
koebnerization.[7]
[11]
Table 1
Keratoacanthomas associated with previous skin graft
|
Author (year)
|
Age/Sex
|
Preceding lesion
|
Time interval between SG and appearance of KA
|
Type of SG
|
Location of KA
|
|
Dibden and Fowler (1955)[a]
|
76/M
|
Keratoacanthoma
|
2 mo
|
Unspecified
|
Donor and Recipient sites
|
|
Wulsin (1958)
|
unspecified
|
Unspecified
|
3 wk
|
Unspecified
|
Donor site
|
|
Schwartz (1979)[a]
|
59/F
|
Keratoacanthoma
|
Unspecified
|
Unspecified
|
Donor site
|
|
Soto-de-Delas et al (1989)
|
38/F
|
Melanoma
|
3 wk
|
Split-thickness
|
Donor site
|
|
Hamilton et al (1997)
|
61/F
|
Burn
|
1 mo
|
Split-thickness
|
Donor site
|
|
Taylor et al (1998)
|
55/M
|
Burn
|
3 wk
|
Split-thickness
|
Donor site
|
|
Tamir et al (1999)
|
54/M
|
Burn
|
4 mo
|
Split-thickness
|
Donor site
|
|
Vergara et al (2007)[a]
|
80/F
|
Keratoacanthoma
|
1 mo
|
Split-thickness
|
Recipient site
|
|
Nagase et al (2016)
|
78/F
|
Actinic Keratosis
|
23 d
|
Full-thickness
|
Donor site
|
|
Nishibaba et al (2017)[a]
|
89/F
|
Keratoacanthoma
|
2 mo
|
Full- thickness
|
Recipient site
|
|
Lee et al (2017)[a]
|
93/F
|
Keratoacanthoma
|
3 mo
|
Split- thickness
|
Donor and Recipient sites
|
|
Our case (2022)
|
57/M
|
Basal cell carcinoma
|
2 wk
|
Full-thickness
|
Recipient site
|
Abbreviations: F, female; KA, keratoacanthoma; M, male; SG, skin graft.
Note: Similar cases are bolded.
a Case of multiple and recurrent KA all around the edge of the skin graft site.
In our case, the KA occurred at the FTSG recipient site following the surgical excision
of a BCC in a relatively young patient. Without dermatological consultation, this
pathogenic presentation may have been misdiagnosed as a SCC and treated invasively
with wide excision margins. Since a possibility of KA regression exists, treatment
with bleomycin Intralesional injection administration can be considered, instead of
surgical resection.[2]
[4] This report presents information that may provide guidance to clinicians performing
dermatologic surgeries and identify better therapeutic strategies. In addition, the
possibility of postoperative KA development should be explained to patients when skin
grafts are used in a surgical site of previous oncogenic insult. Since most of the
previously reported cases developed KA within 2 months, careful follow-up should be
done at least 2 months postoperatively.
