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Research Letters |

Detection of Human Papillomavirus in Multiple Eccrine Poromas in a Patient With Chronic Graft-vs-Host Disease and Immunosuppression FREE

Melissa L. Diamantis, MD; Heather M. Richmond, MD; Peter L. Rady, MD, PhD; Stephen K. Tyring, MD, PhD, MBA; Jonathan E. Cutlan, MD; Carlos Torres-Cabala, MD; Sharon R. Hymes, MD
[+] Author Affiliations

Author Affiliations: The University of Texas Southwestern, Austin (Dr Diamantis); Department of Dermatology (Drs Richmond and Rady), The University of Texas Medical School at Houston (Dr Diamantis); Departments of Dermatology, Microbiology and Molecular Genetics, and Internal Medicine, The University of Texas Health Science Center at Houston (Dr Tyring); and Departments of Pathology (Drs Cutlan and Torres-Cabala) and Dermatology (Drs Torres-Cabala and Hymes), The University of Texas M. D. Anderson Cancer Center, Houston.


Arch Dermatol. 2010;147(1):120-122. doi:10.1001/archdermatol.2010.383.
Text Size: A A A
Published online

A poroma is a benign sweat gland tumor composed of cells with terminal ductal differentiation of either apocrine or eccrine origin. Poromas are usually solitary, slow-growing, skin-colored, sometimes pedunculated papules or plaques. Multiple poromas, or eccrine poromatosis, rarely develop in a widespread distribution: 2 cases of eccrine poromatosis have been reported in the setting of chronic immunosuppression1,2; 3 additional reports document the development of multiple eccrine poromas after external irradiation.35

Our patient developed multiple eccrine poromas after treatment with an allogeneic stem cell transplant with complications of graft-vs-host disease (GVHD) requiring long-term immunosuppression. The poromas were tested for human papillomavirus (HPV) DNA by nested polymerase chain reaction (PCR), and results were positive for beta-HPV. An actinic keratosis and a squamous cell carcinoma (SCC) in situ tested by nested PCR were negative for beta-HPV. To our knowledge, this is the first reported case of HPV positivity in eccrine poromas.

Our patient was a 53-year-old man with a history of mantle cell lymphoma who was treated with an allogeneic stem cell transplant. Over the next 5 years, his posttransplantation course was complicated by chronic GVHD of the skin, mouth, eyes, liver, and gastrointestinal tract, which was managed with photopheresis and immunosuppression with tacrolimus, systemic corticosteroids, and mycophenolate mofetil. He subsequently developed 6 slow-growing, erythematous papules on his palms, heels, and left elbow (Figure 1). The papules ranged in size from 2 to 6 mm, and all were similar in morphologic characteristics except for the pedunculated papule on the elbow.

Place holder to copy figure label and caption
Figure 1.

Erythematous, well-circumscribed plaque on the right heel.

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Biopsy specimens of the right palm, elbow, and left heel demonstrated dome-shaped epidermal proliferations composed of small, cuboidal (“poroid”) cells with basophilic nuclei emanating from the base of the epidermis and extending into the dermis, which are findings characteristic of eccrine poromas (Figure 2). Findings of in situ hybridization studies for low-risk and high-risk alpha-HPV types were negative; however, nested PCR findings for beta-HPV or epidermodysplasia verruciformis (EV) HPV DNA were positive for HPV types 20, 21, and 23 (Figure 3).

Place holder to copy figure label and caption
Figure 2.

Biopsy specimen from our patient. Tumor of epidermal proliferation composed of small, cuboidal and/or basaloid and/or “poroid” cells emanating from the base of the epidermis and extending into the dermis.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Results of nested polymerase chain reaction (PCR) assay. Epidermodysplasia verruciformis (EV) human papillomavirus (HPV) fragments were detected using EV-HPV primer sets in a patient with multiple eccrine poromas. The PCR products were analyzed on 2.0% agarose gel by electrophoresis and visualized on a UV transilluminator. In all panels, lane M represents the ϕX174RF DNA marker (Promega Corporation, Madison, Wisconsin), and lane R represents the reagent control. A, The PCR results generated by EV-HPV primers (second PCR): lane P, EV-HPV positive control DNA (HPV-PCR fragment with the expected size can be seen); lane 1, poroma lesion from left elbow (putative EV-HPV PCR product can be seen); and lane 2, poroma lesion from right palm (putative EV-HPV PCR product can be seen). B, The PCR results generated by EV-HPV primers (second PCR): lane 3, poroma lesion from left heel (putative EV-HPV PCR product can be seen); lane N, EV-HPV–negative DNA; and lane P, EV-HPV–positive control DNA (HPV-PCR fragment with the expected size can be seen). C, The β-globin reference gene PCR assays: lane 1, poroma lesion from left elbow; lane 2, poroma lesion from right palm; lane 3, poroma lesion from left heel; and lane Con, control DNA. The expected β-globin 268–base pair (bp) PCR fragments can be seen in lanes 1, 2, 3, and Con.

Graphic Jump Location

Our patient developed severe multisystem GVHD and multiple HPV-positive eccrine poromas after several years of immunosuppressive therapy, which is the third report to our knowledge of multiple eccrine poromas developing in an immunosuppressed patient. Although we have not found HPV positivity reported in any cases of eccrine poromas, 1 study using immunoper oxidase techniques and bovine papillomavirus type 1 to test poromas reported a negative result for HPV.6

Human papillomaviruses are double-stranded DNA viruses confined to epithelial cells of the skin and mucous membranes of humans. Isolates from the beta-HPV genus exist in latent form in the general population and are activated under conditions of immune suppression. Our patient's lesions tested positive for beta-HPV types 20, 21, and 23, which cause mostly benign cutaneous lesions and are commonly associated with lesions in EV or immunosuppression. Transplant patients are more prone to persistent cutaneous HPV infection, and so in our patient, a combination of long-term immunosuppressive therapy and HPV infection may have collectively contributed to the development of multiple poromas. Beta-HPV was not detected in an actinic keratosis and SCC in situ of the perilesional skin, which is compatible with evidence that beta-HPV may not be merely a “passenger” but rather may play an active role in poroma tumorigenesis. It is interesting to postulate that HPV may have induced the development of multiple poromas. The presence of HPV DNA in the poroma biopsy specimens, however, does not definitively establish a direct causal role. More studies are needed to investigate the molecular mechanism by which HPV infection impacts poroma tumorigenesis.

Correspondence: Dr Diamantis, The University of Texas Southwestern, Austin, PO Box 341752, Austin, TX 78734 (mdiamantis@gmail.com).

Accepted for Publication: June 4, 2010.

Author Contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. Study concept and design: Diamantis, Richmond, Tyring, and Hymes. Acquisition of data: Diamantis, Richmond, Rady, Tyring, Cutlan, Torres-Cabala, and Hymes. Analysis and interpretation of data: Diamantis, Rady, Tyring, Torres-Cabala, and Hymes. Drafting of the manuscript: Diamantis, Torres-Cabala, and Hymes. Critical revision of the manuscript for important intellectual content: Diamantis, Richmond, Rady, Tyring, Cutlan, Torres-Cabala, and Hymes. Statistical analysis: Diamantis. Administrative, technical, and material support: Diamantis, Rady, Tyring, Cutlan, and Torres-Cabala. Study supervision: Diamantis, Richmond, Tyring, and Hymes.

Financial Disclosure: None reported.

Sherman  VReed  JHollowood  KLittlewood  TBurge  SM Poromas and porokeratosis in a patient treated for solid-organ and haematological malignancies. Clin Exp Dermatol 2010;35 (4) e130- e132
PubMed Link to Article
Mahlberg  MJMcGinnis  KSDraft  KSFakharzadeh  SS Multiple eccrine poromas in the setting of total body irradiation and immunosuppression. J Am Acad Dermatol 2006;55 (2) ((suppl)) S46- S49
PubMed Link to Article
Ullah  KPichler  EFritsch  P Multiple eccrine poromas arising in chronic radiation dermatitis. Acta Derm Venereol 1989;69 (1) 70- 73
PubMed
Sidro-Sarto  MGuimerá-Martin-Neda  FPerez-Robayna  N  et al.  Eccrine poroma arising in chronic radiation dermatitis. J Eur Acad Dermatol Venereol 2008;22 (12) 1517- 1519
PubMed Link to Article
Kurokawa  MAmano  MMiyaguni  H  et al.  Eccrine poromas in a patient with mycosis fungoides treated with electron beam therapy. Br J Dermatol 2001;145 (5) 830- 833
PubMed Link to Article
Harvell  JDKerschmann  RLLeBoit  PE Eccrine or apocrine poroma? six poromas with divergent adnexal differentiation. Am J Dermatopathol 1996;18 (1) 1- 9
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Erythematous, well-circumscribed plaque on the right heel.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Biopsy specimen from our patient. Tumor of epidermal proliferation composed of small, cuboidal and/or basaloid and/or “poroid” cells emanating from the base of the epidermis and extending into the dermis.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Results of nested polymerase chain reaction (PCR) assay. Epidermodysplasia verruciformis (EV) human papillomavirus (HPV) fragments were detected using EV-HPV primer sets in a patient with multiple eccrine poromas. The PCR products were analyzed on 2.0% agarose gel by electrophoresis and visualized on a UV transilluminator. In all panels, lane M represents the ϕX174RF DNA marker (Promega Corporation, Madison, Wisconsin), and lane R represents the reagent control. A, The PCR results generated by EV-HPV primers (second PCR): lane P, EV-HPV positive control DNA (HPV-PCR fragment with the expected size can be seen); lane 1, poroma lesion from left elbow (putative EV-HPV PCR product can be seen); and lane 2, poroma lesion from right palm (putative EV-HPV PCR product can be seen). B, The PCR results generated by EV-HPV primers (second PCR): lane 3, poroma lesion from left heel (putative EV-HPV PCR product can be seen); lane N, EV-HPV–negative DNA; and lane P, EV-HPV–positive control DNA (HPV-PCR fragment with the expected size can be seen). C, The β-globin reference gene PCR assays: lane 1, poroma lesion from left elbow; lane 2, poroma lesion from right palm; lane 3, poroma lesion from left heel; and lane Con, control DNA. The expected β-globin 268–base pair (bp) PCR fragments can be seen in lanes 1, 2, 3, and Con.

Graphic Jump Location

Tables

References

Sherman  VReed  JHollowood  KLittlewood  TBurge  SM Poromas and porokeratosis in a patient treated for solid-organ and haematological malignancies. Clin Exp Dermatol 2010;35 (4) e130- e132
PubMed Link to Article
Mahlberg  MJMcGinnis  KSDraft  KSFakharzadeh  SS Multiple eccrine poromas in the setting of total body irradiation and immunosuppression. J Am Acad Dermatol 2006;55 (2) ((suppl)) S46- S49
PubMed Link to Article
Ullah  KPichler  EFritsch  P Multiple eccrine poromas arising in chronic radiation dermatitis. Acta Derm Venereol 1989;69 (1) 70- 73
PubMed
Sidro-Sarto  MGuimerá-Martin-Neda  FPerez-Robayna  N  et al.  Eccrine poroma arising in chronic radiation dermatitis. J Eur Acad Dermatol Venereol 2008;22 (12) 1517- 1519
PubMed Link to Article
Kurokawa  MAmano  MMiyaguni  H  et al.  Eccrine poromas in a patient with mycosis fungoides treated with electron beam therapy. Br J Dermatol 2001;145 (5) 830- 833
PubMed Link to Article
Harvell  JDKerschmann  RLLeBoit  PE Eccrine or apocrine poroma? six poromas with divergent adnexal differentiation. Am J Dermatopathol 1996;18 (1) 1- 9
PubMed Link to Article

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