Table.

Patients’ Characteristics, Intra-anal HPV Spectrum, and HPV DNA Loads Before and After Imiquimod Therapy*

Before Therapy and HPV-16, -18, -31, and HPV-6 and -11 DNA
Clinical
at End of Follow-up -33 DNA Loads† Low-Risk Loads†
Recurrence
Patient High-Risk HPV Types HPV Types After End
Stage After After
No./ of HIV HIV RNA, CD4 Cell First End of First End of Therapy First End of First End of Therapy of Therapy
Age, y Disease‡ Copies/mL Count, /µL Sample Therapy Sample Therapy (mo) Sample Therapy Sample Therapy (mo) (mo)
1/27 A2/B2 12 700/⬍40 251/430 16, 18, 53, 45, 52, 53, 0.1 Neg 2 (9) 6, 43 6 1204 11 189 (9) No (9)
58, 73 58, 73
2/37 A1/A1 23 400/26 400 678/651 16, 73 16, 58, 59, 3 0.003 0.2 (5) 6, 54 Neg 4612 Neg 6 (5) No (5)
73
3/38 A2/A2 30 300/⬍40 552/613 16, 18, 31, 16, 18, 59 64 4 45 (7) 11, 34 11, 40 37 0.9 3 (7) Yes (7)
35, 51,
53, 59,
66, 82
4/26 C3/C3 ⬍40/⬍40 239/291 16, 26, 33, 16, 31, 33, 309 14 4 (2) 11, 72, 42 47 Neg Neg (2) Yes (2)
35, 45 35, 45 84
5/26 C3/C3 ⬍40/61 291/469 16, 18, 39 Neg 0.4 Neg ND 6, 44 6 484 3 ND No follow-up
6/34 C3/C3 ⬍40/⬍40 529/614 16, 18, 31 16, 18, 31, 61 0.1 11 (4) 11 11, 89 6435 0.03 0.43 (4) No (4)
68 35 (8) Yes (8)
7/33 B1/B1 ⬍40/⬍40 672/511 16 16 139 10 0.01 (3) 6, 34 6 295 74 14 (3) No (3)

Abbreviations: HIV, human immunodeficiency virus; HPV, human papillomavirus; ND, not done; Neg, negative.
*Antiretroviral therapy (ART). Patient 1: initially zidovudine, lamivudine, and nevirapine, then emtricitabine, tenofovir, and lopinavir. Patient 2: no ART. Patient 3:
initially no ART, then zidovudine, lamivudine, and nevirapine. Patients 4, 6, and 7: zidovudine, lamivudine, and efavirenz. Patient 5: lopinavir and atazanavir.
†HPV DNA load values are expressed as the number of HPV copies per ␤-globin gene copy.
‡According to staging of the Centers for Disease Control and Prevention, Bethesda, Md.

the use of imiquimod alone.4,8 Application of imiquimod
suppositories after the surgical removal of intra-anal CA
could be a possible treatment option for HIV-positive pa-
tients, although controlled clinical trials in a larger collec-
tive of patients are needed to confirm our encouraging vi-
ral load data and to find out whether relapse rates with the
use of imiquimod after surgery are significantly lower than
with surgery alone. The concomitant reduction of high-
risk HPV DNA loads might also reduce the risk of the de-
velopment of intra-anal intraepithelial neoplasia. Patients
and their partners should be advised to use condoms dur-
ing and after imiquimod therapy to avoid or diminish new
infections with further HPV types and other sexually trans-
mitted pathogens, especially since imiquimod-treated skin
might allow easier entry of sexually transmitted diseases
owing to skin barrier damage.
Alexander Kreuter, MD
Norbert H. Brockmeyer, MD
Soenke J. Weissenborn, PhD
Arasch Wafaisade
Herbert Pfister, PhD
Peter Altmeyer, MD
Ulrike Wieland, MD
for the German Competence Network HIV/AIDS
Correspondence: Dr Kreuter, Department of Dermatol-
ogy, Ruhr-University Bochum, Gudrunstrasse 56,
D-44791 Bochum, Germany (a.kreuter@derma.de).
Financial Disclosure: None.
Funding/Support: This study was supported in part by
the German Competence Network HIV/AIDS (Federal
Ministry of Education and Research, grant 01KI 0211).
1. de Villiers EM, Fauquet C, Broker TR, et al. Classification of papillomaviruses.
Virology. 2004;324:17-27.
2. Dupin N. Genital warts. Clin Dermatol. 2004;22:481-486.
3. Palefsky JM, Holly EA. Chapter 6: immunosupression and co-infection with
HIV. J Natl Cancer Inst Monogr. 2003;31:41-46.
4. De la Fuente SG, Ludwig KA, Mantyh CR. Preoperative immune status de-
termines anal condyloma recurrence after surgical excision. Dis Colon Rectum.
2003;46:367-373.
5. Kaspari M, Gutzmer R, Kaspari T, Kapp A, Brodersen JP. Application of imi-
quimod by suppositories (anal tampons) efficiently prevents recurrences af-
ter ablation of anal canal condyloma. Br J Dermatol. 2002;147:757-759.
6. Kreuter A, Brockmeyer NH, Hochdorfer B, et al. Clinical spectrum and viro-
logic characteristics of anal intraepithelial neoplasia in HIV infection. J Am
Acad Dermatol. 2005;52:603-608.
7. Weissenborn SJ, Funke AM, Hellmich M, et al. Oncogenic human papillomavi-
rus DNA loads in human immunodeficiency virus–positive women with high-
grade cervical lesions are strongly elevated. J Clin Microbiol. 2003;41:2763-2767.
8. Gilson RJ, Shupack JL, Friedman-Kien AE, et al. A randomized, controlled,
safety study using imiquimod for the topical treatment of anogenital warts in
HIV-infected patients. AIDS. 1999;13:2397-2404.
A Seeming Failure of Logic
I am perplexed by what seems to be a contradiction
in conclusions drawn by the members of the Mela-
noma Center at the University of California, San
Francisco, concerning prognosis of primary cutaneous
melanoma. In a recent issue of the ARCHIVES, Shaikh et
al write as follows1(p739):
The presence of microsatellites is intimately tied to other mark-
ers of melanoma aggressiveness. Microsatellites appear to pre-
dict locoregional relapse and RFS [relapse-free survival] but nei-
ther distant metastasis nor OS [overall survival].
However, 4 years ago, in the ARCHIVES, Kashani-Sabet et
al made these statements2(p1172):
The results of our analysis clearly indicate the independent role
of vascular involvement in the prognostic assessment of pa-
tients with melanoma. The presence of vascular involvement
was associated with an increased risk of melanoma relapse and
death. Interestingly, involvement of the tumor vasculature, which
is believed to represent largely lymphatic vessels, was predic-
tive of distant as well as regional nodal metastasis.2
So-called microsatellites come into being as a conse-
quence of “invasion” of cutaneous vessels. In the earlier ar-
ticle, Kashani-Sabet et al2 recognized that the presence of

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244

©2006 American Medical Association. All rights reserved.

vascular involvement is “associated with an increased risk
of melanoma relapse and death,” and, moreover, that it is
“predictive of distant as well as regional nodal metasta-
sis.” How is it possible, having come to that position, that
4 years later they assert that microsatellites appear to pre-
dict locoregional relapse and relapse-free survival but nei-
ther distant metastasis nor overall survival. I would be grate-
ful for an explanation from the authors that weds the 2
seemingly opposing conclusions.
Parenthetically, nearly 20 years ago at New York Uni-
versity, my colleagues and I determined the outcome of
10 patients who presented clinically with only satellite
metastases of melanoma. After 10 years, all were dead of
metastatic melanoma.
A. Bernard Ackerman, MD
Correspondence: Dr Ackerman, 145 E 32nd St, 10th Floor,
New York, NY 10016 (backerman@ameripath.com).
Financial Disclosure: None.
1. Shaikh L, Sagebiel RW, Ferreira CM, Nosrati M, Miller JR III, Kahani-Sabet
M. The role of Microsatellites as a prognostic factor in primary malignant
melanoma. Arch Dermatol. 2005;141:739-742.
2. Kashani-Sabet M, Sagebiel RW, Ferreira CM, Nosrati M, Miller JR III, Wade
TR. Vascular involvement in the prognosis of primary cutaneous melanoma.
Arch Dermatol. 2001;137:1169-1173.
In reply
We appreciate Ackerman’s care in reading our article as
well as the opportunity to clarify the definitions for the dif-
ferent prognostic factors examined in patients with pri-
mary cutaneous melanoma. As indicated in the article’s
“Methods” section,1(p740) microsatellites were
strictly defined as discrete nest(s) of tumor cells distinctly sepa-
rated by a minimum of 0.5 mm (by ocular micrometer) from
the main body (vertical growth phase) of the tumor by a layer of
collagen or subcutaneous fat.
As indicated elsewhere in the “Methods” section, “care was
taken to distinguish between microsatellites and . . . vascular
involvement.”1(p740) The phenomenon of vascular involve-
ment had been previously defined,2 and, owing to space con-
straints, was not redefined in this article. Vascular involve-
ment has been defined to include both (1) vascular invasion,
with tumor cells within the wall or lumens of endothelial-
lined vessels, and (2) uncertain, or incipient vascular inva-
sion, with melanoma cells immediately adjacent to the endo-
thelium, without perithelial cell or fibrous stroma. As strictly
defined and analyzed in these 2 studies, microsatellites are dis-
tinct from vascular involvement (as well as macrosatellites).
In our database, while vascular involvement is an indepen-
dent marker of overall survival (and significantly predictive
of distant metastasis), microsatellitosis is not. Furthermore,
while macrosatellites have been believed to occur as a result
of cutaneous intralymphatic spread, microsatellites, as strictly
defined in this study, do not require this mechanism of cuta-
neous spread.
With respect to the 10 patients with macrosatellites dy-
ing of melanoma, our results appear to confirm the poor prog-
nosis associated with macrosatellites and suggest further that
patients with microsatellites have a better outcome than those
with macrosatellites, strongly suggesting that these 2 phe-
(REPRINTED) ARCH DERMATOL/ VOL 142, FEB 2006
245
©2006 American Medical Association. All rights reserved.
nomena should not be treated as a single entity as man-
dated by the current American Joint Committee on Cancer
staging classification for melanoma.3
Mohammed Kashani-Sabet, MD
Richard W. Sagebiel, MD
Correspondence: Dr Kashani-Sabet, Melanoma Center,
University of California, San Francisco Cancer Center,
1600 Divisadero St, Second Floor, San Francisco, CA
94115 (kashanim@derm.ucsf.edu).
1. Shaikh L, Sagebiel RW, Ferreira CM, Nosrati M, Miller JR III, Kashani-Sabet
M. The role of microsatellites as a prognostic factor in primary malignant
melanoma. Arch Dermatol. 2005;141:739-742.
2. Kashani-Sabet M, Sagebiel RW, Ferreira CM, Nosrati M, Miller JR III. Vas-
cular involvement in the prognosis of primary cutaneous melanoma. Arch
Dermatol. 2001;137:1169-1173.
3. Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint
Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol.
2001;19:3635-3648.
A Psychocutaneous Approach
to Sunbathing Behavior
1
W e applaud the work of Warthan and col-
leagues.1 Their effort to apply an addiction
model to sunbathing behavior illustrates the
benefits of an integrated approach to dermatology that seeks
to find links between the psyche and the soma. However,
we wonder if other models that look at psychological con-
flict and the impact of body image, development, and self-
esteem would also be useful in helping us to understand
those who continue to act in self-destructive ways.
However, regardless of which path we choose as our
focus of research, any attempts to understand the minds
of our patients is sure to lead to more effective treat-
ment interventions.
Matthew Silvan, PhD
Vincent A. DeLeo, MD
Correspondence: Dr Silvan, Psychocutaneous Medi-
cine Clinic, Department of Dermatology, St Luke’s-
Roosevelt Hospital Center, 1090 Amsterdam Ave, 11th
Floor, New York, NY 10025 (mes57@columbia.edu).
Financial Disclosure: None.
1. Warthan MM, Uchida T, Wagner RF. UV light tanning as a type of substance-
related disorder. Arch Dermatol. 2005;141:963-966.
In reply
We appreciate the interest of Silvan and DeLeo in our re-
search. Tanning behavior is likely a complex behavior with
multiple associations, potentially including the psychocu-
taneous factors suggested by these authors. As we learn more
about tanning behavior through additional studies, it is hoped
that effective interventions can be developed.
Molly M. Warthan, MD
Tatsuo Uchida, MS
Richard F. Wagner, MD
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