Patient Report

Yonago Acta medica 2015;58:145–150

Multiple Skin Cancers in a Renal Transplant Recipient: A Patient Report with
Analyses of Human Papillomavirus and Human Polyomavirus Infection
Tokinobu Kaneda,*† Michiko Matsushita,*† Takeshi Iwasaki,† Naoko Ishiguro,* Takashi Koide,‡		Kazuhiko Hayashi† and Yukisato Kitamura**Department of Pathobiological Science and Technology, School of Health Science, Tottori University Faculty of Medicine, Yonago 6838503, Japan, †Division of Molecular Pathology, Department of Pathology, School of Medicine, Tottori University Faculty of Medicine,
Yonago 683-8503, Japan and ‡Department of Dermatology, Yoka Hospital, Yabu 667-8555, Japan

ABSTRACTSkin cancer is an important complication in renal transplant recipients. Associations of transplant-related skintumor with ultraviolet radiation, age at transplantation,
type of immunosuppressant drug administered, and viral infection have been reported; however, the details remain unclear. We report a 61-year-old man who had underwent renal transplantation at 38 years of age and developed multiple skin tumors or squamous cell carcinomas (SCCs). Polymerase chain reaction (PCR) analysesof the patient’s 12 tumors for viral DNAs of cutaneousor mucosal human papillomavirus (HPV) and 6 humanpolyomaviruses (MCPyV, trichodysplasia spinulosaassociated, BK, JC, KI and WU polyomaviruses) only
detected cutaneous HPV-DNA in only 5 of the tumors;no other viruses were detected. Real-time PCR showed
high loads of cutaneous HPV in 3 SCCs and very low
loads of MCPyV in 9. Immunohistochemistry revealedno tumor cell expression for MCPyV-large T-antigen or
mucosal HPV. Our report not only reconfirmed the association of cutaneous HPV5 with skin cancer in renaltransplant recipients in previous studies but also showedno relevant association of 6 human polyomaviruses andmucosal HPV with skin tumors.

in a span of 8 years (approximately 16–23 years after
transplantation) and were examined for viral infection
using PCR, real-time PCR and immunohistochemistry
analyses. We examined the presence of viruses whichhave been reported in skin tumors including Merkel cellpolyomavirus (MCPyV),5 cutaneous human papillomavirus (cutaneous HPV),6 mucosal human papillomavirus(mucosal HPV)7 and trichodysplasia spinulosa-associated polyomavirus (TSPyV).8 Furthermore, we also examined the presence of several polyomaviruses including
BK polyomavirus (BKPyV),9 JC polyomavirus (JCPyV),9KI polyomavirus (KIPyV)10, 11 and WU polyomavirus(WUPyV).12, 13This report presents the patient and the results of examination for viruses previously described with a review
of literature.
PATIENT REPORTThis report was approved by the Institutional Review
Board of Faculty of Medicine, Tottori University,
Yonago 683-8503, Japan.
Patient report

A 61-year-old man who had undergone renal transplantation because of chronic renal failure at 38 years ofage who has since then under been immunosuppressanttherapy with azathioprine and cyclosporine presented ared, dome-shaped, rapidly enlarging tumor on the backof his left hand of 25-mm diameter. The tumor was sur-Key words human papillomavirus; human polyomavirus; polymerase chain reaction renal transplantation;
immunosuppression; skin cancer

Skin cancer is an important complication in renal transplant recipients. Associations with mainly ultraviolet radiation, age at transplantation, type of immunosuppressant drug administered, and viral infection have beenreported,1, 2 although the details remain unclear. Numerous studies have investigated the relationship between
viral infection and skin cancer in renal transplant recipients.3, 4 however, these studies followed the same patient
for several years and only few patients were examined
for multiple viral infections.5, 6 We describe a renaltransplant recipient who repeatedly presented with multiple skin cancers, in particular, squamous cell carcinoma (SCC). Twelve tumors were resected from the patient

Corresponding author: Tokinobu Kaneda
Present Address: Pathological Department, Okayama Kyoritsu General Hospital, Okayama 703-8511, Japankyoutou_no_yabou@yahoo.co.jp
Received 2015 March 17
Accepted 2015 June 25
Abbreviations: BCC, basal cell carcinoma; BCPyV, BC polyomavirus; FFPE, formalin fixed, paraffin embedded; HPV, human papillomavirus; JCPyV, JC polyomavirus; KA, keratoacanthoma; KIPyV, KI polyomavirus; LT, large tumor antigen; MCPyV, Merkel cellpolyomavirus; PCR, polymerase chain reaction; SCC, squamouscell carcinoma; SPF, short PCR fragment; TSPyV, trichodysplasia
spinurosa-associated polyomavirus; VP1, viral protein 1; WUPyV,WU polyomavirus

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T. Kaneda et al.

gically resected, and was histopathologically diagnosed
as keratoacanthoma (KA). The patient had no relevantfamily history (such as epidermodysplasia verruciformis
Lewandowsky-Lutz14), smoking history or occupational
exposure to carcinogens including pitch, tar, and arsenic.
The first onset of skin lesions was 7 years after renaltransplantation, involving multiple tumor formations on
his trunk and limbs. Blood analyses showed no detectable abnormalities except for a slight elevation in lactic
acid dehydrogenase levels (218 IU/L; standard value:
106–211 IU/L). Since then, various skin lesions have occurred, concentrating on the sun-exposed areas, including the head and the forearms (Fig. 1). The lesions weretreated with liquid nitrogen and lesions not effectively
eliminated were surgically excised. Histopathologically,
the lesions consisted of benign tumors such as KA,
verruca vulgaris, Seborrheic keratosis, and malignant
tumors such as SCC in situ, and SCC (Fig. 2). In thiscase, non-typical tumor formation is one of the characteristics. The findings of tumors are not always exactly
like the typically correct findings that are described intext books. Therefore, the pathological findings itself or
descriptive term had to be adapted.

and DNA extraction. DNA was extracted from formalinfixed, paraffin-embedded (FFPE) samples of skin tumors using QIAamp DNA FFPE Tissue Kit (Qiagen,Hilden, Germany), according to the manufacturer’s
protocol. The concentrations of the extracted DNA were
measured using NanoDrop 2000 spectrophotometer(Thermo Fisher Scientific, Waltham, MA).
Immunohistochemstry

To detect MVPyV large tumor antigen (LT) and mucosal HPV viral protein 1 (VP1) antigen, immunohistochemistry was performed using mouse monoclonal antibody CM2B4 (diluted at 1:200; Santa Cruz Biotechnology, Santa Cruz, CA) and mouse monoclonal antibody
K1H8 (1:100; Dako, Glostrup, Denmark) as primary antibody, respectively. Tissue sections were deparaffinizedSamples and DNA extraction

Twelve skin tumors excised from the patient were obtained from the archive of Yoka Hospital (Yabu, Japan).
All cases were reviewed by pathologists, and the diagnoses were confirmed (Table 1). Serial sections of all
samples were used for hematoxylin and eosin staining

3

2

12

6

8
7

4
10

9

1

5
11

Fig. 2. Macroscopic images (a–d) and microscopic
images (e–h) are shown, respectively. a, e-1, e-2, e-3,
tumor of No. 1 (KA); b, f, tumor of No. 12 (Seborrheic
keratosis); c, g, tumor of No. 3 (SCC in situ); d, h, tumorof No. 4 (SCC) (haematoxylin and eosin stain). Bar ofe-1, e-2, e-3, f, 2000 μm; g, h, 500 μm, respectively.
KA, keratoacanthoma; SCC, squamous cell carcinoma.

Fig. 1. Locations of each tumor development. Tumors werefocused on sun-exposed areas including the head and forearm. Macroscopic and microscopic images of tumors areshown at Fig. 2.

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Transplant-associated skin cancer

PCR products were electrophoresed, stained with ethidium bromide, and visualized under UV light using UVP
BioDoc-It System (UVP, Upland, CA).

Table 1. Tumors from the patient
Years after
Size
No. transplantation Location(mm) Diagnosis
Dorsal surface of28
KAright hand
2 20
Forehead
10
SCC
3 20
Right forehead
12
SCC in situ
4 20
Left cheek
16
SCC
Dorsal surface of 15
Verruca vulgaris
5 20
Left 1st digit
6 21
Left outer canthus 10
SCC
7 21
Right lower jaw
13
SCC
8 21
Right side of nose 5
Verruca vulgaris
9 23
Left ear pinna
12
SCC
10 23
Left cheek9
SCC in situ
Dorsal surface of
11 23
20
SCC
left hand
Front surface ofSeborrheic kera12 23
9
tosis
right earKA, keratoacanthoma; SCC, squamous cell carcinoma.
1 16

Sequencing

To determine the sequence of the TaqMan probe usedin quantitative PCR, sequencing was performed before
quantitative PCR because the primers targeting the cutaneous and mucosal HPV were consensus primers foreach type of HPV. The PCR products were purified before sequencing using NucleoSpin Gel and PCR Cleanup (Takara Bio) according to the manufacturer’s protocol. Sequencing was performed using BigDye Terminator v3.1 Cycle Sequencing (Thermo Fisher Scientific)
on an Applied Biosystems 3130XL Genetic Analyzer(Thermo Fisher Scientific), and the resulting DNA sequences were compared against the reference sequencesof GenBank (National Center for Biotechnology Information, National Institute of Health, Bethesda, MD).
The PCR results are shown in Table 3. Cutaneous HPV
was detected in 5 of the 12 sample tumors. Sequence
analysis identified cutaneous HPV as HPV5. MCPyV
was detected in 9 of the 12 sample tumors. DNAs ofmucosal HPV, BKPyV, JCPyV, TSPyV, KIPyV and
WUPyV were not detected in any of the tumor samples.

and rehydrated. Endogenous peroxidase activity was
blocked using 3% hydrogen peroxide for 5 min. Antigen
retrieval was performed by incubating the sections incitrate buffer (pH 6.0) for 10 min at 95 °C. After applying the primary antibody, sections were incubated overnight at 4 °C and then thoroughly washed in phosphatebuffered saline. Peroxidase-conjugated goat anti-mouse
IgG was applied as the secondary antibody. Sections
were incubated for 60 min at room temperature and thenwashed in phosphate-buffered saline. Diaminobenzidine
was used as the chromogen. But no immunoreactivity to
MCPyV and mucosal HPV was detected in any of thetumor samples.

Real-time PCR

To determine MCPyV and cutaneous HPV copy number
in each of the samples examined as positive for these viruses at PCR, real-time PCR was performed using ABI
PRISM 7900HT Sequence Detection System (Thermo
Fisher Scientific). The PCR mixture to determine viral
copy number contained 5.0 pL of THUNDERBIRD
Probe qPCR Mix (Toyobo, Osaka, Japan), 3 pmol of thesame primer pair as that of PCR, 2 pmol of fluoresceinlabeled TaqMan probe, 0.2 pL of 50× ROX reference dye(Toyobo) and 10 ng of genomic DNA, in total volume of
10 pL per sample. The RNAse P gene was used as theinternal control. The PCR mixture to determine RNAse
P copy number contained 5.0 pL of THUNDERBIRD
Probe qPCR Mix (Toyobo), 0.5 pL of 20× TaqMan copy
number reference assay (Thermo Fisher Scientific), 0.2
pL of 50 × ROX reference dye (Toyobo) and 10 ng ofgenomic DNA, in a total volume of 10 pL for each of thesamples. Amplifications consisted of an initial denaturation for 1 min at 95 °C and 45 cycles of denaturation for
15 sec at 95 °C, annealing for 45 sec at 60 °C. Standard
curves were drawn using positive controls of each of
the viruses. The results of quantitative PCR analysis areshown in Table 4. TaqMan probes used in real-time PCR
consisted of the universal probe library 22 (for MCPyV)and universal probe library 35 (for HPV 5), respectively.

PCR
To detect viral DNA in each tumor sample, PCR was
carried out using primers described elsewhere.8–13, 15–18
The PCR products were approximately 100 base pairsin length (Table 2). To detect mucosal HPV, a mixture ofshort PCR fragment (SPF) 1A, 1B, 1C and 1D was used
as forward primer and a mixture of SPF2B and 2D asreverse primer. PCR was performed using 0.25 U of TaKaRa Ex Taq HS (Takara Bio, Ohtsu, Japan), 2.5 pmolof each deoxyribonucleoside triphosphate, 2.0 pmol
Mg2+, 5 pmol of each primer pair and 10 ng of genomic
DNA, generating a total volume of 10 pL per sample.
Amplifications consisted of an initial denaturation for 4
min at 95 °C and 40 cycles of denaturation for 30 s at 95°C, annealing for 30 s at 52 °C (for SPF primers) or at 59°C (for the other primers), an extension step for 1 min at
72 °C and then, and a final extension for 4 min at 72 °C.
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T. Kaneda et al.
Table 2. Primers for PCR
Virus
Protein

Product (bp)

Sequence (5’–3’)

MCPyV

LT

76

Mucosal HPV

VP1

66

Cutaneous HPV

E1

117

BKPyV

VP1

127

JCPyV

VP1

101

TSPyV

NCCR

103

VP1

143

LT

121

KIPyV

VP1

100

WUPyV

LT

77

F: AGGTTGACGAGGCCCCTAT
R: TTCCCGAAGCTGAATCCTCSPF1A: GCICAGGGICACAATAATGG
SPF1B: GCICAGGGICATAACAATGG
SPF1C: GCICAGGGICATAATAATGG
SPF1D: GCICAAGGICATAATAATGG
SPF2B: GTIGTATCIACAACAGTAACAAASPF2D: GTIGTATCIACTACAGTAACAAA
F: ACTGACCAAAGCTGGAAATC
R: TCTTGCAGAGCATTGAAACG
F: GCAGCTCCCAAAAAGCCAAA
R: CTGGGTTTAGGAAGCATTCTAF: AGAAAAGGAGAAAGGAAGGACCC
R: TCTGTAATTGAGTCAACCCCAGTTT
F: TCATACTGCCACAAACACAGGAAG
R: AGAACACAGAGCGGGAGGATG
F: AGTCTAAGGACAACTATGGTTACAG
R: ATTACAGGTTAGGTCCTCATTCAAC
F: TGTGTTTGGAAACCAGAATCATTTG
R: TGCTACCTTGCTATTAAATGTGGAG
F: GGAAATACAGCTGCTCAGGAT
R: CTTTGATACTTGAACCGCTTTCCTT
F: TGTTGCATCCATTTGTTACATTCA
R: GAAAGAACTGTTAGACAAATATATAG

E1, E1 protein; F, forward; HPV, human papillomavirus; JCPyV, JC polyomavirus; KIPyV, KI polyomavirus; LT, large tumor antigen;
NCCR, non-coding control region; PCR, polymerase chain reaction; R, reverse; SPF, short PCR fragment; VP1, viral protein 1; WUPyV,WU polyomavirus.

Table 3. The results of PCR for viral DNAsTSPyVNo. Diagnosis
BKPyV JCPyV
NCCR

VP1

LT

1
2
3
4
5
6
7
8
9
10
11
12

–
–
–
–
–
–
–
–
–
–
–
–

–
–
–
–
–
–
–
–
–
–
–
–

KA
SCC
SCC in situ
SCC
Verruca vulgaris
SCC
SCC
Verruca vulgaris
SCC
SCC in situ
SCC
Seborrheic keratosis

–
–
–
–
–
–
–
–
–
–
–
–

–
–
–
–
–
–
–
–
–
–
–
–

–
–
–
–
–
–
–
–
–
–
–
–

KIPyV

WUPyV MCPyV

Mucosal Cutaneous
HPV
HPV

–
–
–
–
–
–
–
–
–
–
–
–

–
–
–
–
–
–
–
–
–
–
–
–

–
–
–
–
–
–
–
–
–
–
–
–

–
–
+
+
+
+
+
+
–
+
+
+

–
+
+
+
–
–
–
–
–
–
+
+

BCPyV, BC polyomavirus; HPV, human papillomavirus; JCPyV JC polyomavirus; KA, keratoacanthoma; KIPyV, KI polyomavirus; LT,large tumor antigen; MCPyV, Merkel cell polyomavirus; NCCR, non-coding control region; SCC, squamous cell carcinoma; TSPyV,trichodysplasia spinurosa-associated polyomavirus; VP1, viral protein 1; WUPyV, WU polyomavirus.

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Transplant-associated skin cancer

Large copy numbers of HPV 5 were observed in 3 (No.
3, 4 and 11) of the 12 tumor samples, and very low copy
numbers of MCPyV were detected in 9 of 12 samples.

the characteristic. The findings of tumors are not always
correctly typical findings which are described in the
text books. Therefore, the pathological findings itself
or descriptive term had to be adapted (ex. SCC in situ).
Neoplastic lesions developed on sun-exposed area. Thissuggests that the sun exposure is one of the importantfactor of tumor formation. In addition, we assumed thatviral infection is another important factor coming from
immunosuppression. Then we examined for viral effects
using PCR assay and immunohistochemical assay.
At first, we tried immunohistochemical assay;
however, since significant results were not obtained, we
carried out PCR assay. The high viral load of cutaneous
HPV (HPV5) was detected in 3 of the 12 tumors. HPV5
has been often detected in skin cancer in renal transplant
recipients; Barr et al.6 detected HPV5/8 in 15 (60%) of
25 SCCs from 202 renal allograft recipients who had
undergone kidney transplantations and were monitored
over 3 years. In our case, although cutaneous HPV was
not necessarily detected in all tumors, all 3 tumors fromwhich cutaneous HPV was detected were SCCs, suggesting that cutaneous HPV affects the development ofskin cancer rather than the incidence.
In terms of the association of MCPyV with skincancer in renal transplant recipients, Mertz et al.6 examined 17 renal transplant recipients and 3 patients
under long-term dialysis with skin tumors and detected
MCPyV-DNA by PCR in 2 patients with Bowen’s disease. On the other hand as for MCPyV in nontumor tissue, Matsushita et al. reported that MCPyV is prevalentin humans and was detected most frequently in the skinof 41 autopsy cases.24 We detected MCPyV-DNA in
9 of 12 samples. But MCPyV is considered to have no
relation to tumorigenesis in our patient, since their copy
numbers were very low.
In terms of the relationship between the type of
immunosuppressant and the incidence of skin cancer,
previous studies have shown that patients immunosuppressed with azathioprine and cyclosporine showed
higher rates of skin cancer than those on tacrolimus,20, 23
although the finer details are currently under scrutiny.
Our data suggests that there is a relationship between cutaneous HPV in skin cancer and renal transplantation. Cutaneous HPV is influenced by other factors such as ultraviolet radiation, which increases theincidence and the development of skin cancer in renaltransplant recipients.
Rogers et al.25 reported acquired epidermodysplasia
verruciformis (epidermodysplasia verruciformis like
syndrome). There is a common background such as immunodeficiency. However, in this case, tumors are notalways flat warts (verruca plana), and few reports about

Table 4. The result of quantitative real-time PCR analysis
MCPyV
Cutaneous HPV
No. Diagnosis(copy/cell)(copy/cell)
1 KA
–
–
2 SCC
–
ND
3 SCC in situ
0.000482
1.83
4 SCC
0.00340
146.0
5 Verruca vulgaris
0.0000531–
6 SCC
0.00500–
7 SCC
0.00103–
8 Verruca vulgaris
0.000329
–
9 SCC
–
–
10 SCC in situ
0.00306–
11 SCC
0.000286
1.69
12 Seborrheic keratosis 0.0466
ND–, not tested because negative at PCR; HPV, human papillomavirus; KA, keratoacanthoma; MCPyV, Merkel cell polyomavirus;
ND, not detected; SCC, squamous cell carcinoma.

DISCUSSION
Skin cancer is an important complication in renal transplant recipients. Incidence varies according to geographic latitudes; Naldi et al.19 reported that the incidence wasapproximately 5% after 5 years and 10% after 10 years
in Italy. Bouwes et al.20 reported an incidence of 3%
after 5 years and 16% after 11 years in Netherlands, and
25% after 5 years and 45% after 11 years in Australia.
These results suggest the association of ultraviolet radiation with skin cancer in renal transplant recipients. In
the population undergoing transplantation, the standardized morbidity ratio compared with immunocompetentpeople is 60–250 times for SCC and 10–40 times forbasal cell carcinoma (BCC).21 In addition, the SCC:BCC
ratio is reversed compared with the ratio of 1:4 in the
immunocompetent people.
In Japan, the incidence of skin cancer is low. Arichi
et al.22 examined 429 renal transplant recipients for 25
years and reported 9 cases (2%) of skin cancers. On theother hand, Imao et al.23 (2007) reported the overall incidence of malignancy in renal transplant recipients was
6.8% (25/366 patients); however, no skin cancer cases
have been documented in this population.
In the present report, we examined 12 tumors froma 61-year-old man who previously underwent renaltransplantation and presented with multiple skin cancers. In this case, non-typical tumor formation is one of149

T. Kaneda et al.

a very long follow up of many and multiple tumor formation in the same patient after renal transplantation,
as this case, is observed. Therefore, the relation of thiscase to acquired epidermodysplasia verruciformis is notalways clear. Further studies are needed to better understand the etiology of this malignancy.

10 Mourez T, Bergeron A, Ribaud P, Scieux C, de Latour RP,
Tazi A, et al. Polyomaviruses KI and WU in immunocompromised patients with respiratory disease. Emarg Infect Dis.
2009;15:107-9. PMID: 19116066.
11 Allander T, Andreasson K, Gupta S, Bjerkner A, Bogdanovic G,
Persson MA, et al. Identification of a third human polyomavirus. J Virol. 2007;81:4130-6. PMID: 17287263.
12 Le BM, Demertzis LM, Wu G, Tibbets RJ, Buller R,
Arens MQ, et al. Clinical and epidemiologic characterization of WU polyomavirus infection. Emerg Infect Dis.
2007;13:1936-8. PMID: 18258052.
13 Gaynor AM, Nissen MD, Whiley DM, Mackay IM,
Lambert SB, Wu G, et al. Identification of a novel polyomavirus from patients with acute respiratory tract infections. PLoS
Pathog. 2007;3:e64. PMID: 17480120.
14 Orth G. Genetics of epidermodysplasia verruciformis: Insights
into host defense against papillomaviruses. Semin Immunol.
2006;18:362-74. PMID: 17011789.
15 Yamaguchi S, Niwa R, Kazuki Y, Ohbayashi T. Applicationof a bacterial artificial chromosome modification system fora human artificial chromosome vector. Yonago Acta Med.
2011;54:21-31. PMID: 2403112.
16 Kuwamoto S, Higaki H, Kanai K, Iwasaki T, Sano H,
Nagata K, et al. Association of Merkel cell polyomavirus
infection with morphologic differences in Merkel cell carcinoma. Hum Pathol. 2011;42:632-40. PMID: 21277612.
17 Kleter B, van Doorn LJ, ter Schegget J, Schrauwen L,
van Krimpen K, Burger M, et al. Novel short-fragment PCR
assay for highly sensitive broad-spectrum detection of anogenital human papillomaviruses. Am J Pathol. 1998;153:17319. PMID: 9846964.
18 de Koning M, Quint W, Struijk L, Kleter B, Wanningen P,
van Doorn LJ, et al. Evaluation of a novel highly sensitive,
broad-spectrum PCR-reverse hybridization assay for detection
and identification of beta-papillomavus DNA. J Clin Microbiol. 2006;44:1792-800. PMID: 16672409.
19 Naldi L, Fortina AB, Lovati S, Barba A, Gotti E, Tessari G,
et al. Risk of nonmelanoma skin cancer in Italian organtransplant recipients A registry-based study. Transplantation.
2000;70:1479-84. PMID: 11118094.
20 Bouwes Bavinck JN, Hardie DR, Green A, Cutmore S,
MacNaught A, O’Sullivan V, et al. The risk of skin cancer inrenal transplant recipients in Queensland, Australia A followup study. Transplantation. 1996;61:715-21. PMID: 8607173.
21 Tessari G, and Giromoni G. Nonmelanoma skin cancer insolid organ transplant recipients: update on epidemiology, risk
factors, and management. Dermatol Surg. 2012;38:1622-30.
PMID: 22805312.
22 Arichi N, Kishikawa H, Nishimura K, Mitsui Y, Namba Y,
Tokugawa S, et al. Malignancy following kidney transplantation. Transplant Proc. 2008;40:2400-2. PMID: 18790247.
23 Imao T, Ichimaru N, Takahara S, Kokado Y, Okumi M,
Imamura R, et al. Risk factors for malignancy in Japanese
renal transplant recipients. Cancer. 2007;109:2109-15. PMID:
17407138.
24 Matsushita M, Kuwamoto S, Iwasaki T, Higaki-Mori H,
Yashima S, Kato M, et al. Detection of Merkel cell polyomavirus in the human tissues from 41 Japanese autopsy cases
using polymerase chain reaction. Intervirology. 2013;56:1-5.
PMID: 22986833.
25 Roger HD, MacGregor JL, Nord KM, Tyring S, Rady P,
Engler DE, et al. Acquired epidermodysplasia verruciformis. J
Am Acad Dermatol. 2009;60:315-20. PMID: 19150275.

Acknowledgments: We are grateful to Associate Professor I. Murakami, Dr. M. Kato, Dr. K. Nagata, Dr. S. Kuwamoto, Mr. H.
Sugihara, Ms. H. Sugihara, Division of Molecular Pathology, andall other members of Department of Pathobiological Science andTechnology, Tottori University Faculty of Medicine; Professor E.
Nanba, Ms. K. Adachi, Ms. M. Nomura and all other members of
the Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, for their useful advises
and excellent technical supports.
The authors declare no conflict of interest.

REFERENCES
1 Serdar ZA, Eren PA, Canbakan EM, Turan K, Tellioglu G,
Gülle S, et al. Dermatologic findings in renal transplant recipients: possible effects of immunosuppression regimen andp53 mutations. Transplant Proc. 2002;42:2538-41 PMID:
20832539.
2 Proby CM, Harwood CA, Neale RE, Green AC, Euvrard S,
Naldi L, et al. A case-control study of betapapillomavirus
infection and cutaneous squamous cell carcinoma in organtransplant recipients. Am J Transplant. 2011;11:1498-508.
PMID: 21718442.
3 Dworkin, AM, Tseng SY, Allain DC, Iwenofu OH, Peters SB,
Toland AE. Merkel cell polyomavirus in cutaneous squamouscell carcinoma of immunocompetent individuals. J Invest
Dermatol. 2009;129:2868-74. PMID: 19554019.
4 Purdie KJ, Surentheran T, Sterling JC, Bell L, McGregor JM,
Proby CM, et al. Human papillomavirus gene expression
in cutaneous squamous cell carcinomas from immunosuppressed and immunocompetent individuals. J Invest Dermatol.
2005;125:98-107. PMID: 15982309.
5 Mertz KD, Pfaltz M, Junt T, Schmid M, Fernandez Figueras MT,
Pfaltz K, et al. Merkel cell polyomavirus is present in common warts and carcinoma in situ of the skin. Hum Pathol.
2010;41:1369-79. PMID: 20655089.
6 Barr BB, Benton EC, McLaren K, Bunney MH, Smith IW,
Blessing K, et al. Human papilloma virus infection and skincancer in renal allograft recipients. Lancet. 1989;333:124-9.
PMID: 2563048.
7 Zheng S, Adachi A, Shimizu M, Shibata SI, Yasue S,
Sakakibara A, et al. Human papillomaviruses of the mucosal
type are present in some cases of extragenital Bowen’s disease. Br J Dermatol. 2005;152:1243-7. PMID: 15948988.
8 v a n d e r M e i j d e n E , J a n s s e n s RW, L a u b e r C ,Bouwes Bavinck JN, Gorbalenya AE, Feltkamp MC. Discovery of a new human polyomavirus asociated with trichodysplasia spinulosa in an immunocompiromized patient. PLoS
Pathog. 2010;6:e1001024. PMID: 20686659.
9 Husseiny MI, Anastasi B, Singer J, Lacey SF. A comparative
study of Merkel cell, BK and JC polyomavirus infections inrenal transplant recipients and healthy subjects. J clin Virol.
2010;49:137-40. PMID: 20667770.

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