Chang, Ya-Ching

Hsiao, Wen-Chin

Ko, Jui-Hung

Kuan, Yue-Zon

Kuo, Tseng-tong

Tseng, Fang-Wen

Wu, Yi-Fang

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DERMATOLOGICA SINICA 29 (2011) 144–146Contents lists availableDermatologica Sinica
journal homepage: http: / /www.derm-sinica.comCORRESPONDENCE
Large cell acanthoma manifesting as multiple white papules on extremitiesCase reports
Case 1
A39-year-oldwomanwith essential hypertension anddiabetesmel-
litus presented with multiple asymptomatic white papules on herFigure 1 (A) A 39-year-old woman with multiple whitish papules on her upper extremit
1027-8117/$ – see front matter Copyright  2011, Taiwanese Dermatological Association
doi:10.1016/j.dsi.2011.09.015bilateral upper extremities for more than 10 years. They were small
well-deﬁned, ﬂat-topped white papules measuring 0.2–0.5 cm
(Figure 1A). A skin biopsy taken from her left upper arm showed
basket weave hyperkeratosis and awell-demarcated area of slightly
thickened epidermis composed of enlarged cells with nuclei larger
than those of the adjacent normal epidermal cells (Figure 2A).ies. (B) Scattered depigmented papules on the extremities in a 38-year-old woman.
. Published by Elsevier Taiwan LLC. All rights reserved.
Figure 2 (A) Case 1. Microscopic details show basket weave hyperkeratosis and acan-
thosis with enlarged keratinocytes compared to the adjacent epidermal cells (enlarged
in inset). (B) Case 2. The skin shows hyperkeratosis, acanthosis composed of large ker-
atinocytes with large nuclei (enlarged in inset). Both skins are depigmented.
Table 1 The relationship between human papillomavirus (HPV) and large cell
acanthomas.
Case Reference Method HPV type
1. Berger et al4 PCR 6
2. Garrido-Rios et al5 PCR 16,53
3. Present case Present case PCR 33
PCR¼ polymerase chain reaction.
Correspondence / Dermatologica Sinica 29 (2011) 144–146 145Case 2
A 38-year-old woman presented with multiple asymptomatic
white papules on her four extremities for 6 months. They were
well-demarcated and slightly elevated white papules measuring
0.5 cm (Figure 1B). The number of these lesions was increasing
gradually over a 2-month period. A skin biopsy taken from her
left upper arm showed a focal slightly elevated lesion with
moderate hyperkeratosis and thickened epidermis composed of
larger epidermal cells with enlarged nuclei, and mild perivascular
mononuclear cell inﬁltration in the dermis (Figure 2B).
Discussion
In 1970, Pinkus1 reported large cell acanthoma (LCA) as epidermal
lesions with epidermal orthokeratosis with or without papilomato-
sis; the size of the keratinocytes was at least twice as large as that of
the nearby normal keratinocytes. Sanchez Yus et al2 proposed that
LCA was a disease entity which was different from solar lentigo.
Unlike solar lentigo, the keratinocytes in LCA were deﬁnitely larger
than normal ones and hyperkeratosis was also a distinct feature.
Different deoxyribonucleic acid (DNA) content was demonstrated
in LCA and solar lentigo by Rabinowitz et al.3As to the pathogenesis of LCA, human papillomavirus (HPV) has
been reported to be associatedwith LCA (Table 1).4,5 In 2005, Berger
et al4 claimed that HPV type 6 might be associated with LCA
because it was detected on lesional skin by using polymerase chain
reaction (PCR). Garrido-Rios et al5 demonstrated HPV type 16 in
conjunction with HPV type 53 not only in lesional skin but also in
perilesional skin in 2009. In Case 1, we found HPV type 33 by the
PCR-based gene chip method. However, in Case 2, no HPV was
detected. Besides, no uniform HPV type is found in the reports
mentioned above. The relationship between HPV infection and
LCA remains to be investigated.
Clinically, LCA presents as a single or multiple hyperpigmented
papules, usually less than 10 mm in size.2–4 The clinical differential
diagnosis includes solar lentigo, Bowen’s disease, actinic keratosis,
and seborrheic keratosis.2,3 Achromic LCA is unusual and one case
of a verrucous papule on right hand has been reported.6 The clinical
manifestation of the generalized depigmented papules on limbs
had not been reported before. Clear cell papulosis could be a clinical
differential diagnosis for multiple depigmented papules on the
trunk and/or limbs. Histopathological examinations could help to
establish the deﬁnite diagnosis.
The histological features of LCA can be classiﬁed into three
patterns as basic, verrucous and hyperkeratotic.2 In our cases, the
basic pattern is favored. Classically, the pathological ﬁndings were
characterized by acanthosis, hyperkeratosis, and epidermal cells
with abundant cytoplasm and larger round nuclei.3 Basal pigmen-
tation is one of the features in typical LCA, but our two cases are
depigmented.
To date, there was no deﬁnite treatment modality for multiple
LCAs. Because LCA is usually a solitary lesion, an excisional biopsy
achieves both therapeutic and examining goals. In Case 1, the
patient was treated with topical retinoid and then trichloroacetic
acid (TCA), while the other patient received topical corticosteroids.
Only TCA gained therapeutic effect, but recurrence of skin lesions
was also noted. More therapeutic trials for this entity need to be
explored.
In summary, we report two cases of LCA presented as multiple
depigmented papules on the extremities. They should be consid-
ered in the differential diagnosis of similar clinical lesions. Our
results of HPV study raises further question for the role of HPV in
the pathogenesis of LCA.Yi-Fang Wu, Jui-Hung Ko
Department of Dermatology, Chang Gung Memorial Hospital, Taipei, Taiwan
Chang Gung University, College of Medicine, Taiwan
Tseng-tong Kuo
Department of Pathology, Chang Gung Memorial Hospital, Taipei, Taiwan
Chang Gung University, College of Medicine, Taiwan
Ya-Ching Chang*, Fang-Wen Tseng, Wen-Chin Hsiao, Yue-Zon Kuan
Department of Dermatology, Chang Gung Memorial Hospital, Taipei, Taiwan
Chang Gung University, College of Medicine, Taiwan
*Corresponding author. Ya-Ching Chang,
No. 199, Tunghwa North Road, Taipei, Taiwan.
Tel.: þ886 2 2713 5211; fax: þ886 2 2719 1623.
E-mail address: ycchang@adm.cgmh.org.tw (Y.-C. Chang).
Correspondence / Dermatologica Sinica 29 (2011) 144–146146References
1. Pinkus H. Epidermal mosaic in benign and precancerous neoplasia (with special
reference to large-cell acanthoma). Acta Dermatol (Kyoto) 1970;65:75–81.
2. Sanchez Yus E, del Rio E, Requena L. Large-cell acanthoma is a distinctive condi-
tion. Am J Dermatopathol 1992;14:140–7.
3. Rabinowitz AD, Inghirami G. Large-cell acanthoma. A distinctive keratosis. Am J
Dermatopathol 1992;14:136–8.
4. Berger T, Stockﬂeth E, Meyer T, et al. Multiple disseminated large-cell acantho-
mas of the skin associated with human papillomavirus type 6. J Am Acad Derma-
tol 2005;53:335–7.5. Garrido-Rios AA, Sanz-Munoz C, Aragoneses-Fraile MH, et al. Human papilloma-
virus detection in multiple large-cell acanthomas. J Eur Acad Dermatol Venereol.
2009;23:454–5.
6. Ambrojo P, Aguilar A, Requena L, et al. Achromic verrucous large cell acanthoma.
J Cutan Pathol 1990;17:182–4.Received: Jan 28, 2011
Revised: Feb 23, 2011
Accepted: Mar 16, 2011


Large cell acanthoma manifesting as multiple white papules on extremities 

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Large cell acanthoma manifesting as multiple white papules on extremities

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