A 61-year-old man presented with multiple small, reddish, eroded papules located on his chest (Figure 1A). Histopathologic examination revealed the typical findings of Grover\u2019s disease

Argenziano, Giuseppe

Lallas, Aimilios

Longo, Caterina

Moscarella, Elvira

Specchio, Francesca

Tiodorovic-Zivkovic, Danica

Zalaudek, Iris

Dermatology Practical & Conceptual

PubMed

Francesca Specchio

Giuseppe Argenziano

Danica Tiodorovic-Zivkovic

Elvira Moscarella

Aimilios Lallas

Iris Zalaudek

Caterina Longo

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Observation  |  Dermatol Pract Concept 2015;5(1):11 59
DERMATOLOGY PRACTICAL & CONCEPTUAL
www.derm101.com
Case presentations
Case 1
A 61-year-old man presented with multiple small, reddish, 
eroded papules located on his chest (Figure 1A). Histo-
Dermoscopic clues to diagnose 
acantholytic dyskeratosis
Francesca Specchio1, Giuseppe Argenziano2, Danica Tiodorovic-Zivkovic3, Elvira Moscarella2, 
Aimilios Lallas2, Iris Zalaudek4, Caterina Longo2
1 Department of Dermatology, University of Rome, Tor Vergata, Italy
2 Dermatology and Skin Cancer Unit, Arcispedale S. Maria Nuova, IRCCS, Reggio Emilia, Italy
3 Clinic of Dermatovenerology, Clinical Center of Nis, Medical Faculty, University of Nis, Serbia
4 Department of Dermatology, Medical Universiy of Graz, Graz, Austria
Key words: acantholytic dyskeratosis, dermoscopy
Citation: Specchio F, Argenziano G, Tiodorovic-Zivkovic D, Moscarella E, Lallas A, Zalaudek I, Longo C. Dermoscopic clues to diagnose 
acantholytic dyskeratosis. Dermatol Pract Concept 2015;5(1):11. doi: 10.5826/dpc.05011
Received: September 8, 2014; Accepted: October 16, 2014; Published: January 30, 2015
Copyright: ©2015 Specchio 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 made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data. Drs. 
Specchio and Longo wrote the manuscript. All authors revised it critically for important intellectual content. All authors gave the final 
approval of this version to be published.
Corresponding author: Caterina Longo, MD, PhD, Dermatology and Skin Cancer Unit, Arcispedale Santa Maria Nuova-IRCCS, Viale 
Risorgimento, 80, 42100 Reggio Emilia, Italy. Tel. 390522295612; Fax. 390594224271. Email: longo.caterina@gmail.com
Figure 1. (A) Clinical examination of case 1 showed multiple confluent erythematous papules in a patient with Grover’s disease. (B) Clini-
cally, multiple reddish papules were observed on the chest of a patient with stage IV melanoma treated with vemurafenib. (Copyright: ©2015 
Specchio et al.)
pathologic examination revealed the typical findings of 
Grover’s disease.
Case 2
A 47-year-old woman was treated with vemurafenib for stage 
60 Observation  |  Dermatol Pract Concept 2015;5(1):11
benign and malignant lesions, such as cutaneous squamous-
cell carcinoma, verrucal keratosis, plantar hyperkeratosis, 
hair follicle changes, panniculitis, and photosensitivity [2], 
along with widespread eruptions with histologic features of 
acantholytic dyskeratosis [3]. Acantholytic dyskeratoma has 
been previously reported in association with other chemo-
therapeutics, including the epidermal growth factor receptor 
inhibitor cetuximab; however, the pathogenesis of acantho-
lytic dyskeratosis is still unclear. Two hypotheses have been 
postulated. One theory is that the accumulation in the skin 
of chemotherapy metabolites by sweating may be related to 
the development of dyskeratosis and acantholysis; another 
theory supposes that acantholytic dyskeratosis may represent 
an off-target effect of small-molecule kinase inhibitors [1].
Recognition of cutaneous side effects occurring during 
BRAF-inhibitor therapy is essential for patient management. 
Acantholytic dyskeratomas can be easily diagnosed by using 
dermoscopy. In fact, in acantholytic lesions, dermoscopy 
allows the visualization of a stereotypical pattern [4], which 
also assists in the differentiation of these benign lesions from 
malignancy, such as keratoacanthoma or invasive squamous 
cell carcinoma that may also occur as a complication of 
BRAF inhibitor therapy. Typically, these papules display a 
central star-like pattern of brown scales that are otherwise 
not detectable at clinical examination. This dermoscopic 
pattern has been described to be peculiar for Grover’s disease 
and solitary acantholytic dyskeratoma [4]. Interestingly, our 
study shows the characteristic dermoscopic star-like pattern 
can be observed in acantholytic dyskeratotic lesions occur-
ring during treatment with BRAF-inhibitors, as previously 
reported [3].
In conclusion, our case underlines the importance of der-
moscopy to improve the recognition of acantholytic dyskera-
tomas (in Grover’s disease and in patients under vemurafenib 
therapy), a skin eruption that is usually difficult to diagnose 
by naked eye.
References
1.  Gupta M, Huang V, Linette G, Cornelius L. Unusual complication 
of vemurafenib treatment of metastatic melanoma: exacerbation 
of acantholytic dyskeratosis complicated by Kaposi varicelliform 
eruption. Arch Dermatol 2012;148(8):966-68.
2.  Anforth R, Fernandez-Peñas P, Long GV. Cutaneous toxicities of 
RAF inhibitors. Lancet Oncol 2013;14(1):e11-8.
3.  Chu EY, Wanat KA, Miller CJ, et al. Diverse cutaneous side effects 
associated with BRAF inhibitor therapy: A clinicopathologic study. 
J Am Acad Dermatol 2012;67(6):1265-72.
4.  Giacomel J, Zalaudek I, Argenziano G. Dermatoscopy of Grover’s 
disease and solitary acantholytic dyskeratoma shows a brown, 
star-like pattern. Australas J Dermatol 2012;53(4): 315-16.
IV melanoma, having been referred because of the recent 
onset of multiple asymptomatic reddish papules located on 
her chest (Figure 1B). These lesions represented a skin rash 
of acantholytic dyskeratoma occurring while under vemu-
rafenib treatment that spontaneously disappeared over the 
next few weeks.
The dermoscopic evaluation of the lesions in both cases 
showed a central yellowish to brown star-like pattern over-
lying a pinkish homogeneous structureless area (Figure 2A 
and B).
Conclusions
Treatment with vemurafenib, a small-molecule BRAF inhib-
itor, has led to significant improvement of prognosis in 
patients with advanced melanoma. Similar to other kinase 
inhibitors, the use of vemurafenib has been accompanied by 
several dermatologic adverse events [1]. These include both 
Figure 2. (A) Dermoscopic evaluation of case 1 displayed a central 
yellowish to brown star-like pattern overlying a pinkish homoge-
neous structureless area similarly to the ones observed in case 2 (B). 
(Copyright: ©2015 Specchio et al.)


Dermoscopic clues to diagnose acantholytic dyskeratosis

A 61-year-old man presented with multiple small, reddish, eroded papules located on his chest (Figure 1A). Histopathologic examination revealed the typical findings of Grover’s disease

Archivio istituzionale della ricerca - Università di Trieste

Observation  |  Dermatol Pract Concept 2015;5(1):11 59DERMATOLOGY PRACTICAL & CONCEPTUALwww.derm101.comCase presentationsCase 1A 61-year-old man presented with multiple small, reddish, eroded papules located on his chest (Figure 1A). Histo-Dermoscopic clues to diagnose acantholytic dyskeratosisFrancesca Specchio1, Giuseppe Argenziano2, Danica Tiodorovic-Zivkovic3, Elvira Moscarella2, Aimilios Lallas2, Iris Zalaudek4, Caterina Longo21 Department of Dermatology, University of Rome, Tor Vergata, Italy2 Dermatology and Skin Cancer Unit, Arcispedale S. Maria Nuova, IRCCS, Reggio Emilia, Italy3 Clinic of Dermatovenerology, Clinical Center of Nis, Medical Faculty, University of Nis, Serbia4 Department of Dermatology, Medical Universiy of Graz, Graz, AustriaKey words: acantholytic dyskeratosis, dermoscopyCitation: Specchio F, Argenziano G, Tiodorovic-Zivkovic D, Moscarella E, Lallas A, Zalaudek I, Longo C. Dermoscopic clues to diagnose acantholytic dyskeratosis. Dermatol Pract Concept 2015;5(1):11. doi: 10.5826/dpc.05011Received: September 8, 2014; Accepted: October 16, 2014; Published: January 30, 2015Copyright: ©2015 Specchio 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 made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data. Drs. Specchio and Longo wrote the manuscript. All authors revised it critically for important intellectual content. All authors gave the final approval of this version to be published.Corresponding author: Caterina Longo, MD, PhD, Dermatology and Skin Cancer Unit, Arcispedale Santa Maria Nuova-IRCCS, Viale Risorgimento, 80, 42100 Reggio Emilia, Italy. Tel. 390522295612; Fax. 390594224271. Email: longo.caterina@gmail.comFigure 1. (A) Clinical examination of case 1 showed multiple confluent erythematous papules in a patient with Grover’s disease. (B) Clini-cally, multiple reddish papules were observed on the chest of a patient with stage IV melanoma treated with vemurafenib. (Copyright: ©2015 Specchio et al.)pathologic examination revealed the typical findings of Grover’s disease.Case 2A 47-year-old woman was treated with vemurafenib for stage 60 Observation  |  Dermatol Pract Concept 2015;5(1):11benign and malignant lesions, such as cutaneous squamous-cell carcinoma, verrucal keratosis, plantar hyperkeratosis, hair follicle changes, panniculitis, and photosensitivity [2], along with widespread eruptions with histologic features of acantholytic dyskeratosis [3]. Acantholytic dyskeratoma has been previously reported in association with other chemo-therapeutics, including the epidermal growth factor receptor inhibitor cetuximab; however, the pathogenesis of acantho-lytic dyskeratosis is still unclear. Two hypotheses have been postulated. One theory is that the accumulation in the skin of chemotherapy metabolites by sweating may be related to the development of dyskeratosis and acantholysis; another theory supposes that acantholytic dyskeratosis may represent an off-target effect of small-molecule kinase inhibitors [1].Recognition of cutaneous side effects occurring during BRAF-inhibitor therapy is essential for patient management. Acantholytic dyskeratomas can be easily diagnosed by using dermoscopy. In fact, in acantholytic lesions, dermoscopy allows the visualization of a stereotypical pattern [4], which also assists in the differentiation of these benign lesions from malignancy, such as keratoacanthoma or invasive squamous cell carcinoma that may also occur as a complication of BRAF inhibitor therapy. Typically, these papules display a central star-like pattern of brown scales that are otherwise not detectable at clinical examination. This dermoscopic pattern has been described to be peculiar for Grover’s disease and solitary acantholytic dyskeratoma [4]. Interestingly, our study shows the characteristic dermoscopic star-like pattern can be observed in acantholytic dyskeratotic lesions occur-ring during treatment with BRAF-inhibitors, as previously reported [3].In conclusion, our case underlines the importance of der-moscopy to improve the recognition of acantholytic dyskera-tomas (in Grover’s disease and in patients under vemurafenib therapy), a skin eruption that is usually difficult to diagnose by naked eye.References1.  Gupta M, Huang V, Linette G, Cornelius L. Unusual complication of vemurafenib treatment of metastatic melanoma: exacerbation of acantholytic dyskeratosis complicated by Kaposi varicelliform eruption. Arch Dermatol 2012;148(8):966-68.2.  Anforth R, Fernandez-Peñas P, Long GV. Cutaneous toxicities of RAF inhibitors. Lancet Oncol 2013;14(1):e11-8.3.  Chu EY, Wanat KA, Miller CJ, et al. Diverse cutaneous side effects associated with BRAF inhibitor therapy: A clinicopathologic study. J Am Acad Dermatol 2012;67(6):1265-72.4.  Giacomel J, Zalaudek I, Argenziano G. Dermatoscopy of Grover’s disease and solitary acantholytic dyskeratoma shows a brown, star-like pattern. Australas J Dermatol 2012;53(4): 315-16.IV melanoma, having been referred because of the recent onset of multiple asymptomatic reddish papules located on her chest (Figure 1B). These lesions represented a skin rash of acantholytic dyskeratoma occurring while under vemu-rafenib treatment that spontaneously disappeared over the next few weeks.The dermoscopic evaluation of the lesions in both cases showed a central yellowish to brown star-like pattern over-lying a pinkish homogeneous structureless area (Figure 2A and B).ConclusionsTreatment with vemurafenib, a small-molecule BRAF inhib-itor, has led to significant improvement of prognosis in patients with advanced melanoma. Similar to other kinase inhibitors, the use of vemurafenib has been accompanied by several dermatologic adverse events [1]. These include both Figure 2. (A) Dermoscopic evaluation of case 1 displayed a central yellowish to brown star-like pattern overlying a pinkish homoge-neous structureless area similarly to the ones observed in case 2 (B). (Copyright: ©2015 Specchio et al.)

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Dermoscopic clues to diagnose acantholytic dyskeratosis

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