Argenziano, Giuseppe

Jerković Gulin, Sandra

Jurakić Tončić, Ružica

Kostović, Krešimir

Radoš, Jaka

Štulhofer Buzina, Daška

Dermatology Practical & Conceptual

University of Zagreb Medical School Repository

204 Letter  |  Dermatol Pract Concept 2018;8(3):11DERMATOLOGY PRACTICAL & CONCEPTUALwww.derm101.comDigital dermatoscopy as a useful tool for evaluating therapeutic efficacy in a patient with eruptive keratoacanthomasRuzica Jurakic Toncic1, Sandra Jerkovic Gulin2, Jaka Rados1, Daska Stulhofer Buzina1,  Kresimir Kostovic1, Giuseppe Argenziano31 Department of Dermatology and Venereology, University Hospital Centre Zagreb, Zagreb School of Medicine, Zagreb, Croatia2 Department of Infectious Diseases, Dermatology, and Venereology, General Hospital Sibenik, Sibenik, Croatia3 Dermatology Unit, University of Campania, Naples, ItalyKey words: digital dermoscopy follow-up, keratoacanthoma, eruptive keratoacanthomas, treatment response to acitretinCitation: Jurakic Toncic R, Jerkovic Gulin S, Rados J, Stulhofer Buzina D, Kostovic K, Argenziano G. Digital dermoscopy as useful tool for evaluating therapeutic efficacy in a patient with eruptive keratoacanthomas. Dermatol Pract Concept. 2018;8(3):204-207. DOI: https:/ doi.org/10.5826/dpc.0803a11Received: September 25, 2017; Accepted: March 7, 2018; Published: July 31, 2018Copyright: ©2018 Jurakic Toncic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Funding: None.Competing interests: The authors have no conflicts of interest to disclose.All authors have contributed significantly to this publication.Corresponding author: Ruzica Jurakic Toncic, MD, Department of Dermatology and Venereology, University Hospital Centre Zagreb, Salata 4, 10000, Zagreb, Croatia. Email: rjtoncic@gmail.com.IntroductionDigital dermoscopy follow-up (DDFU) has proved its place in the monitoring of patients with multiple moles. The main indications for DDFU are a large number of nevi, a personal/familial history of melanoma, and patients with lesions where excision would lead to disfiguring scars. DDFU includes short-term (3-6 months) and long-term (6-12 months) follow-up strategies [1,2]. Keratoacanthoma (KA) is a relatively common, rapidly growing low-grade tumor that originates in the pilosebaceous glands and closely resembles squamous cell carcinoma (SCC) [3]. Some authors regard KA as a vari-ant of SCC [4]. KA rapidly grows within few weeks/months, followed by spontaneous resolution within few months. Rarely, cases of KA progressing to invasive/metastatic car-cinoma have been reported. Trauma, human papilloma virus, genetic factors, immunosuppression, professional expo-sure to carcinogens, and some drugs have been considered in etiology of KA [3,5]. Infrequently, KA presents as multiple tumors, and there are few described syndromes with multiple KAs including Grzybowski syndrome (generalized eruptive KA; hundreds of papules in middle-aged adults) [6], Muir-Torre/Lynch syndrome (skin tumors in association with vis-ceral cancer) [7], Ferguson-Smith syndrome (rare autosomal dominant disorder characterized by the sudden appearance of multiple self-healing recurrent skin tumors resembling well-differentiated SCC/KA in young age) [8], and KA centrifugum marginatum [9]. Authors speculate that multiple KA might belong to the spectrum of keratinocytes maturation abnor-malities, giving a clue for acitretin therapy [10].Case PresentationWe report a case of a 78-year-old man with multiple eruptive KA-like tumors generalized on the body. Face, palms, soles, Letter  |  Dermatol Pract Concept 2018;8(3):11 205and mucosa were spared. The patient reported the occurrence of tumors within 3 months before the first visit. His family members did not present with skin tumors. Physical examination revealed the presence of up to 50 well-demarcated, dome-shaped nodules with a rolled, mildly erythematous border and central hyperkeratotic plug (Fig-ure 1). Most of the lesions were less than 0.5 cm in diameter with only a few more than 1 cm in diameter. Der-matoscopy revealed a central mass of yellow-white keratin with some hem-orrhages, peripheral arrangement of hairpin vessels, linear vessels, and, less commonly, glomerular vessels. Biopsy of several lesions was done, and in most we confirmed KA and in just 4 cases we confirmed SCC (Figure 2). All histologi-cally proven SCC underwent complete surgical excision.After surgery, acitretin  50  mg/day was administered, subsequently reduced to 30 mg/day after a month due to nonspecific bone/muscle pain. Figure 1. Clinical findings. (A) A large number of well-demarcated, dome-shaped nodules with a rolled, mildly erythematous border and central hyperkeratotic plug on the back (be-fore the treatment). (B) The total count of lesions was reduced and signs of regression were present, resulting in loss of palpability. [Copyright: ©2018 Jurakic Toncic et al.]Figure 2. Histopathology of lesions before and during acitretin treatment. (A) and (B) Lesions excised before acitretin treatment. Well-differentiated squamous cell carcinoma (medium power photomicrograph, hema-toxylin and eosin [H&E] stain ×4), intra-dermal tumor islands of pleomorphic kera-tinocytes at the base of tumor accompanied by a marked inflammatory infiltrate with eosinophils (high-power photomicrograph, H&E stain ×20). (C) Lesions excised before acitretin treatment. Small and well-demar-cated lesion with characteristic crateriform architecture with symmetrical overhanging edges of epidermal hyperplasia and central keratin plug (H&E stain ×2). (D) Regress-ing/resolving phase of keratoacanthoma un-der treatment. Histopathology revealed flat-tening of cup shape of the lesion, irregular hyperplastic epidermis without atypia of ke-ratinocytes, solitary dyskeratotic keratino-cytes, fibrosis, and angioplasia with mixed infiltrate of inflammatory cells reminiscent on scar tissue (medium power photomicro-graph, H&E stain ×4). Biopsy was done dur-ing the treatment. [Copyright: ©2018 Jura-kic Toncic et al.]206 Letter  |  Dermatol Pract Concept 2018;8(3):11Upon submission of the article, acitretin treatment was still ongoing, and the patient was being closely moni-tored, dermoscopically and clinically, with dermoscopic documentation com-pleted every 2 months. Detailed diag-nostic investigations had been excluded visceral malignancy until now. At the time of submission, the patient was on a regimen of acitretin 25 mg/day, but with few new lesions observed. We decided to keep the patient on this dosage because he could not stand the pain that came with a higher dosage. The complete duration of the therapy was 6 months at the time of submission of the arti-cle. The patient was monitored from the aspect of skin and visceral tumors, An excellent therapeutic response was seen very quickly, after only 10 days of therapy, with good resolution of all tumors after 2 months. Resolution of the lesion was histologically proven (Figure 2). Full-body photography and dermoscopic images of most of the lesions were taken before the treatment. At the 2-month follow-up, an excel-lent treatment response was observed. Observation found no new lesions and signs of regression in all lesions, result-ing in loss of palpability, loss of atypical vessels, loss of keratin structures, and the presence of melanophages/peppering structures (Figure 3). This is comparable to the finding seen in histology report of the regressed lesion (Figure 2).Figure  3. Dermatoscopic images taken with digital dermoscopy system VisioMed micro-DERM D120, equipped with full-body documentation system with SLR camera Canon EOS 1200 D. (A), (C), and (E) Lesions before the acitretin treatment. (A) Hyperkeratotic, ver-rucous lesion with nonspecific vessels with the adjunction of seborrheic keratosis in the lower part. Atypical vessels and hyperkeratotic lesions are present in other lesions before treatment. (B), (D), and (F) The same lesions at 2-month follow-up, during treatment. Almost complete regression of the lesions along with loss of nodularity and signs of regression (peppering sign and nonspecific erythema) are observed. Loss of atypical vessels, loss of keratin structures, and the presence of melanophages/peppering structures present phenomena detected in other lesions after the treatment. [Copyright: ©2018 Jurakic Toncic et al.]and the examinations were repeated on a 6-month basis.ConclusionsDDFU has proven efficacy in the follow-up of patients with multiple nevi. In our case, DDFU proved to be very useful because it allowed documentation of the efficacy of acitretin therapy, regression of the previously observed lesions, and follow-up of the possible occurrence of new lesions. As the patient developed new lesions on a lowered dose, we sug-gest that DDFU can also be used as an additional tool for finding the lowest and most optimal dose that might be used to prevent the development of new lesions.References 1. Moscarella E, Tion I, Zalaudek I, et al. Both short-term and long-term dermos-copy monitoring is useful in detecting melanoma in patients with multiple atypical nevi. J Eur Acad Dermatol Vene-reol. 2017;31(2):247-251. doi: 10.1111/jdv.13840. 2. Longo C, Borsari S, Benati E, Moscarella E, Alfano R, Argenziano G. Dermoscopy and reflectance confocal microscopy for monitoring the treatment of actinic kera-tosis with ingenol mebutate gel: report of two cases. Dermatol Ther (Heidelb). 2016;6(1):81-87. doi: 10.1007/s13555-016-0094-9. 3. Kwiek B, Schwartz RA. Keratoacantho-ma (KA): an update and review. J Am Acad Dermatol. 2016;74(6):1220-1233. doi: 10.1016/j.jaad.2015.11.033. 4. Ogita A, Ansai SI, Misago N, Anan T, Fukumoto T, Saeki H. Histopathologi-cal diagnosis of epithelial crateriform tumors: keratoacanthoma and other epithelial crateriform tumors. J Der-matol. 2016;43(11):1321-1331. doi: 10.1111/1346-8138.13390. 5. Sinha R, Larkin J, Gore M, Fearfield L. Cutaneous toxicities associated with ve-murafenib therapy in 107 patients with BRAF V600E mutation-positive meta-static melanoma, including recognition and management of rare presentations. Br J Dermatol. 2015;173(4):1024-1031. doi: 10.1111/bjd.13958.Letter  |  Dermatol Pract Concept 2018;8(3):11 207treated with acitretin. Clin Exp Dermatol. 2010;35(4):e100-e102. doi: 10.1111/j.1365-2230.2009.03668.x. 9. Divers AK, Correale D, Lee JB. Keratoacanthoma centrifugum marginatum: a diagnostic and therapeutic challenge. Cutis. 2004;73(4):257-262.10. Farro P, Zalaudek I, Ferrara G, et al. Unusual association between acrokeratosis verruciformis of Hopf and multiple keratoacantho-mas. Successful therapy with acitretin. J Dtsch Dermatol Ges. 2004;2(6):440-442. 6. Laaff H, Mittelviefhaus H, Wokalek H, Schöpf E. Grzybowski type eruptive keratoacanthomas and ectropion. A therapeutic problem. Hautarzt. 1992;43(3):143-147. 7. Hartig C, Stieler W, Stadler R. Muir-Torre syndrome. Diagnostic criteria and review of the literature. Hautarzt. 1995;46(2):107-113. doi: 10.1007/s001050050218. 8. Robertson SJ, Bashir SJ, Pichert G, Robson A, Whittaker S. Severe exacerbation of multiple self-healing squamous epithelioma (Fer-guson-Smith disease) with radiotherapy, which was successfully 

Digital dermatoscopy as a useful tool for evaluating therapeutic efficacy in a patient with eruptive keratoacanthomas

Ruzica Jurakic Toncic

Sandra Jerkovic Gulin

Jaka Rados

Daska Stulhofer Buzina

Kresimir Kostovic

Giuseppe Argenziano

Directory of Open Access Journals

204 Letter  |  Dermatol Pract Concept 2018;8(3):11
DERMATOLOGY PRACTICAL & CONCEPTUAL
www.derm101.com
Digital dermatoscopy as a useful tool for 
evaluating therapeutic efficacy in a patient with 
eruptive keratoacanthomas
Ruzica Jurakic Toncic1, Sandra Jerkovic Gulin2, Jaka Rados1, Daska Stulhofer Buzina1,  
Kresimir Kostovic1, Giuseppe Argenziano3
1 Department of Dermatology and Venereology, University Hospital Centre Zagreb, Zagreb School of Medicine, Zagreb, Croatia
2 Department of Infectious Diseases, Dermatology, and Venereology, General Hospital Sibenik, Sibenik, Croatia
3 Dermatology Unit, University of Campania, Naples, Italy
Key words: digital dermoscopy follow-up, keratoacanthoma, eruptive keratoacanthomas, treatment response to acitretin
Citation: Jurakic Toncic R, Jerkovic Gulin S, Rados J, Stulhofer Buzina D, Kostovic K, Argenziano G. Digital dermoscopy as useful tool for 
evaluating therapeutic efficacy in a patient with eruptive keratoacanthomas. Dermatol Pract Concept. 2018;8(3):204-207. DOI: https:/ 
doi.org/10.5826/dpc.0803a11
Received: September 25, 2017; Accepted: March 7, 2018; Published: July 31, 2018
Copyright: ©2018 Jurakic Toncic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are 
credited.
Funding: None.
Competing interests: The authors have no conflicts of interest to disclose.
All authors have contributed significantly to this publication.
Corresponding author: Ruzica Jurakic Toncic, MD, Department of Dermatology and Venereology, University Hospital Centre Zagreb, 
Salata 4, 10000, Zagreb, Croatia. Email: rjtoncic@gmail.com.
Introduction
Digital dermoscopy follow-up (DDFU) has proved its place 
in the monitoring of patients with multiple moles. The main 
indications for DDFU are a large number of nevi, a personal/
familial history of melanoma, and patients with lesions where 
excision would lead to disfiguring scars. DDFU includes 
short-term (3-6 months) and long-term (6-12 months) follow-
up strategies [1,2]. Keratoacanthoma (KA) is a relatively 
common, rapidly growing low-grade tumor that originates 
in the pilosebaceous glands and closely resembles squamous 
cell carcinoma (SCC) [3]. Some authors regard KA as a vari-
ant of SCC [4]. KA rapidly grows within few weeks/months, 
followed by spontaneous resolution within few months. 
Rarely, cases of KA progressing to invasive/metastatic car-
cinoma have been reported. Trauma, human papilloma 
virus, genetic factors, immunosuppression, professional expo-
sure to carcinogens, and some drugs have been considered in 
etiology of KA [3,5]. Infrequently, KA presents as multiple 
tumors, and there are few described syndromes with multiple 
KAs including Grzybowski syndrome (generalized eruptive 
KA; hundreds of papules in middle-aged adults) [6], Muir-
Torre/Lynch syndrome (skin tumors in association with vis-
ceral cancer) [7], Ferguson-Smith syndrome (rare autosomal 
dominant disorder characterized by the sudden appearance of 
multiple self-healing recurrent skin tumors resembling well-
differentiated SCC/KA in young age) [8], and KA centrifugum 
marginatum [9]. Authors speculate that multiple KA might 
belong to the spectrum of keratinocytes maturation abnor-
malities, giving a clue for acitretin therapy [10].
Case Presentation
We report a case of a 78-year-old man with multiple eruptive 
KA-like tumors generalized on the body. Face, palms, soles, 
Letter  |  Dermatol Pract Concept 2018;8(3):11 205
and mucosa were spared. The patient 
reported the occurrence of tumors 
within 3 months before the first visit. 
His family members did not present 
with skin tumors. Physical examination 
revealed the presence of up to 50 well-
demarcated, dome-shaped nodules with 
a rolled, mildly erythematous border 
and central hyperkeratotic plug (Fig-
ure 1). Most of the lesions were less 
than 0.5 cm in diameter with only a 
few more than 1 cm in diameter. Der-
matoscopy revealed a central mass of 
yellow-white keratin with some hem-
orrhages, peripheral arrangement of 
hairpin vessels, linear vessels, and, less 
commonly, glomerular vessels. Biopsy 
of several lesions was done, and in most 
we confirmed KA and in just 4 cases we 
confirmed SCC (Figure 2). All histologi-
cally proven SCC underwent complete 
surgical excision.
After surgery, acitretin  50  mg/
day was administered, subsequently 
reduced to 30 mg/day after a month 
due to nonspecific bone/muscle pain. 
Figure 1. Clinical findings. (A) A large number of well-demarcated, dome-shaped nodules 
with a rolled, mildly erythematous border and central hyperkeratotic plug on the back (be-
fore the treatment). (B) The total count of lesions was reduced and signs of regression were 
present, resulting in loss of palpability. [Copyright: ©2018 Jurakic Toncic et al.]
Figure 2. Histopathology of lesions before 
and during acitretin treatment. (A) and (B) 
Lesions excised before acitretin treatment. 
Well-differentiated squamous cell carcinoma 
(medium power photomicrograph, hema-
toxylin and eosin [H&E] stain ×4), intra-
dermal tumor islands of pleomorphic kera-
tinocytes at the base of tumor accompanied 
by a marked inflammatory infiltrate with 
eosinophils (high-power photomicrograph, 
H&E stain ×20). (C) Lesions excised before 
acitretin treatment. Small and well-demar-
cated lesion with characteristic crateriform 
architecture with symmetrical overhanging 
edges of epidermal hyperplasia and central 
keratin plug (H&E stain ×2). (D) Regress-
ing/resolving phase of keratoacanthoma un-
der treatment. Histopathology revealed flat-
tening of cup shape of the lesion, irregular 
hyperplastic epidermis without atypia of ke-
ratinocytes, solitary dyskeratotic keratino-
cytes, fibrosis, and angioplasia with mixed 
infiltrate of inflammatory cells reminiscent 
on scar tissue (medium power photomicro-
graph, H&E stain ×4). Biopsy was done dur-
ing the treatment. [Copyright: ©2018 Jura-
kic Toncic et al.]
206 Letter  |  Dermatol Pract Concept 2018;8(3):11
Upon submission of the article, 
acitretin treatment was still ongoing, 
and the patient was being closely moni-
tored, dermoscopically and clinically, 
with dermoscopic documentation com-
pleted every 2 months. Detailed diag-
nostic investigations had been excluded 
visceral malignancy until now. At the 
time of submission, the patient was on a 
regimen of acitretin 25 mg/day, but with 
few new lesions observed. We decided to 
keep the patient on this dosage because 
he could not stand the pain that came 
with a higher dosage. The complete 
duration of the therapy was 6 months 
at the time of submission of the arti-
cle. The patient was monitored from 
the aspect of skin and visceral tumors, 
An excellent therapeutic response was 
seen very quickly, after only 10 days 
of therapy, with good resolution of all 
tumors after 2 months. Resolution of 
the lesion was histologically proven 
(Figure 2). Full-body photography and 
dermoscopic images of most of the 
lesions were taken before the treatment. 
At the 2-month follow-up, an excel-
lent treatment response was observed. 
Observation found no new lesions and 
signs of regression in all lesions, result-
ing in loss of palpability, loss of atypical 
vessels, loss of keratin structures, and 
the presence of melanophages/peppering 
structures (Figure 3). This is comparable 
to the finding seen in histology report of 
the regressed lesion (Figure 2).
Figure  3. Dermatoscopic images taken with digital dermoscopy system VisioMed micro-
DERM D120, equipped with full-body documentation system with SLR camera Canon 
EOS 1200 D. (A), (C), and (E) Lesions before the acitretin treatment. (A) Hyperkeratotic, ver-
rucous lesion with nonspecific vessels with the adjunction of seborrheic keratosis in the lower 
part. Atypical vessels and hyperkeratotic lesions are present in other lesions before treatment. 
(B), (D), and (F) The same lesions at 2-month follow-up, during treatment. Almost complete 
regression of the lesions along with loss of nodularity and signs of regression (peppering sign 
and nonspecific erythema) are observed. Loss of atypical vessels, loss of keratin structures, 
and the presence of melanophages/peppering structures present phenomena detected in other 
lesions after the treatment. [Copyright: ©2018 Jurakic Toncic et al.]
and the examinations were repeated on 
a 6-month basis.
Conclusions
DDFU has proven efficacy in the follow-
up of patients with multiple nevi. In our 
case, DDFU proved to be very useful 
because it allowed documentation of the 
efficacy of acitretin therapy, regression 
of the previously observed lesions, and 
follow-up of the possible occurrence of 
new lesions. As the patient developed 
new lesions on a lowered dose, we sug-
gest that DDFU can also be used as an 
additional tool for finding the lowest 
and most optimal dose that might be 
used to prevent the development of new 
lesions.
References
 1. Moscarella E, Tion I, Zalaudek I, et al. 
Both short-term and long-term dermos-
copy monitoring is useful in detecting 
melanoma in patients with multiple 
atypical nevi. J Eur Acad Dermatol Vene-
reol. 2017;31(2):247-251. doi: 10.1111/
jdv.13840.
 2. Longo C, Borsari S, Benati E, Moscarella 
E, Alfano R, Argenziano G. Dermoscopy 
and reflectance confocal microscopy for 
monitoring the treatment of actinic kera-
tosis with ingenol mebutate gel: report 
of two cases. Dermatol Ther (Heidelb). 
2016;6(1):81-87. doi: 10.1007/s13555-
016-0094-9.
 3. Kwiek B, Schwartz RA. Keratoacantho-
ma (KA): an update and review. J Am 
Acad Dermatol. 2016;74(6):1220-1233. 
doi: 10.1016/j.jaad.2015.11.033.
 4. Ogita A, Ansai SI, Misago N, Anan T, 
Fukumoto T, Saeki H. Histopathologi-
cal diagnosis of epithelial crateriform 
tumors: keratoacanthoma and other 
epithelial crateriform tumors. J Der-
matol. 2016;43(11):1321-1331. doi: 
10.1111/1346-8138.13390.
 5. Sinha R, Larkin J, Gore M, Fearfield L. 
Cutaneous toxicities associated with ve-
murafenib therapy in 107 patients with 
BRAF V600E mutation-positive meta-
static melanoma, including recognition 
and management of rare presentations. 
Br J Dermatol. 2015;173(4):1024-1031. 
doi: 10.1111/bjd.13958.
Letter  |  Dermatol Pract Concept 2018;8(3):11 207
treated with acitretin. Clin Exp Dermatol. 2010;35(4):e100-e102. 
doi: 10.1111/j.1365-2230.2009.03668.x.
 9. Divers AK, Correale D, Lee JB. Keratoacanthoma centrifugum 
marginatum: a diagnostic and therapeutic challenge. Cutis. 
2004;73(4):257-262.
10. Farro P, Zalaudek I, Ferrara G, et al. Unusual association between 
acrokeratosis verruciformis of Hopf and multiple keratoacantho-
mas. Successful therapy with acitretin. J Dtsch Dermatol Ges. 
2004;2(6):440-442.
 6. Laaff H, Mittelviefhaus H, Wokalek H, Schöpf E. Grzybowski 
type eruptive keratoacanthomas and ectropion. A therapeutic 
problem. Hautarzt. 1992;43(3):143-147.
 7. Hartig C, Stieler W, Stadler R. Muir-Torre syndrome. Diagnostic 
criteria and review of the literature. Hautarzt. 1995;46(2):107-
113. doi: 10.1007/s001050050218.
 8. Robertson SJ, Bashir SJ, Pichert G, Robson A, Whittaker S. Severe 
exacerbation of multiple self-healing squamous epithelioma (Fer-
guson-Smith disease) with radiotherapy, which was successfully 


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Digital dermatoscopy as a useful tool for evaluating therapeutic efficacy in a patient with eruptive keratoacanthomas

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