[Skip to Content]
Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
[Skip to Content Landing]
Table.  
Detection of Cutavirus DNA in Primary Cutaneous B- and T-Cell Lymphomasa
Detection of Cutavirus DNA in Primary Cutaneous B- and T-Cell Lymphomasa
1.
Mirvish  JJ, Pomerantz  RG, Falo  LD  Jr, Geskin  LJ.  Role of infectious agents in cutaneous T-cell lymphoma: facts and controversies.  Clin Dermatol. 2013;31(4):423-431.PubMedGoogle ScholarCrossref
2.
Phan  TG, Dreno  B, da Costa  AC,  et al.  A new protoparvovirus in human fecal samples and cutaneous T cell lymphomas (mycosis fungoides).  Virology. 2016;496:299-305.PubMedGoogle ScholarCrossref
3.
Swerdlow  SH, Campo  E, Pileri  SA,  et al.  The 2016 revision of the World Health Organization classification of lymphoid neoplasms.  Blood. 2016;127(20):2375-2390.PubMedGoogle ScholarCrossref
4.
Herberhold  S, Hellmich  M, Panning  M,  et al.  Human polyomavirus and human papillomavirus prevalence and viral load in non-malignant tonsillar tissue and tonsillar carcinoma.  Med Microbiol Immunol. 2017;206(2):93-103.PubMedGoogle ScholarCrossref
5.
Väisänen  E, Fu  Y, Hedman  K, Söderlund-Venermo  M.  Human protoparvoviruses.  Viruses. 2017;9(11):E354.PubMedGoogle ScholarCrossref
Research Letter
August 2018

Cutavirus Infection in Primary Cutaneous B- and T-Cell Lymphoma

Author Affiliations
  • 1Department of Dermatology, Venerology and Allergology, HELIOS St Elisabeth Hospital Oberhausen, University Witten/Herdecke, Oberhausen, Germany
  • 2Institute of Pathology, Mülheim an der Ruhr, Mülheim, Germany
  • 3Institute of Virology, National Reference Center for Papilloma-and Polyomaviruses, University of Cologne, Cologne, Germany
JAMA Dermatol. 2018;154(8):965-967. doi:10.1001/jamadermatol.2018.1628

For decades, infectious agents, in particular viruses, have been postulated as potential antigenic stimulators in the pathogenesis of primary cutaneous lymphomas, leading to clonal expansion of T-cells and malignant transformation.1 However, all of the so far suspected viruses including retroviruses, herpesviruses, and polyomaviruses have failed to reveal a consistent association with both cutaneous B-cell lymphoma (CBCL) and cutaneous T-cell lymphoma (CTCL).1 Recently, a novel parvovirus named cutavirus was discovered in human fecal samples and in 4 lesional biopsy specimens of patients with mycosis fungoides (MF).2 Therefore, we initiated a retrospective virological study to screen for the presence of cutavirus DNA in a large number of lesional skin samples from patients with different types of CBCL and CTCL.

Methods

A total of 189 paraffin-embedded biopsy specimens from 130 patients with CBCL or CTCL were analyzed (Table). All tumors were classified according to the current World Health Organization/European Organization for Research and Treatment of Cancer classification system for cutaneous lymphomas.3 Samples were analyzed by real-time polymerase chain reaction (PCR) for the presence of cutavirus DNA using primers 5′-AACCAAACACACCGAACCAG-3′ and 5′-TGAAAAGGCTTACCTCTTTTGG-3′ with locked nucleic acid probe No. 5 (Roche) and PCR conditions as described.4 The specificity of the PCR was confirmed by sequence analysis. Cutavirus DNA load was defined as viral DNA copies per β-globin gene copy. The study was approved by the ethics review board of the University Witten/Herdecke.

Results

Cutavirus DNA was found in 6 (3.2%) of 189 lymphoma biopsies and in 6 (4.6%) of 130 patients (Table). Cutavirus was exclusively detected in patients with MF and was absent in all patients with other types of lymphoma (6 of 71 [8.5%; 95% CI, 3.9%-17.2%] vs 0 of 59 [0%; 95% CI, 0%-6.1%], P = .03; Fisher exact test) (Table). All cutavirus-positive patients were male and had early stage MF (IA or IB). In the cutavirus-positive samples, viral DNA loads ranged between 1.3 and 85.0 cutavirus DNA copies per β-globin gene copy (Table).

Discussion

All previous attempts to identify an infectious origin in cutaneous lymphoma have yielded conflicting results.1 Several human parvoviruses have been isolated recently, among them cutavirus in 2016.2,5 Some of them have been detected in cancer tissue (eg, parvovirus B19 in thyroid carcinomas, bocavirus in lung and colorectal cancers).2,5 In a recent study, cutavirus DNA was found in 4 (23.5%) of 17 CTCL samples, whereas 31 non-CTCL samples (eg, eczema, parapsoriasis, skin cancer) were PCR negative. In situ hybridization revealed only few cutavirus-positive cells located in the upper spinal layer of 2 CTCL samples, but not in the infiltrating neoplastic T cells.2 In an ongoing study of our group, cutavirus DNA was found in 4% of skin swabs of over 200 healthy individuals, which is similar to the cutavirus DNA positivity rate found in the present study. These observations argue against a pathogenic role of cutavirus in cutaneous lymphoma. Possibly, cutavirus is similar to β human papillomaviruses and some polyomaviruses, a constituent of the human skin microbiome. In line with this, parvovirus B19 is still detectable in skin biopsy samples years after initial infection.2 Nevertheless, we cannot exclude a role of cutavirus in a small subset of MF cases.

Our findings should be interpreted in light of the limitations of the study. Although a relatively large number of samples were analyzed, the number of rare lymphoma subtypes was small for most tumor groups. For some lymphoma subtypes no biopsy samples were available. Moreover, in most patients only a single lesional specimen was available, possibly underestimating the true prevalence of cutavirus. By analyzing a large number of samples, our observations argue against a pathogenic role of cutavirus in most primary cutaneous lymphomas.

Back to top
Article Information

Corresponding Author: Alexander Kreuter, MD, Department of Dermatology, Venerology and Allergology, HELIOS St Elisabeth Hospital Oberhausen, University Witten/Herdecke, Josefstr 3, 46045 Oberhausen, Germany (alexander.kreuter@helios-kliniken.de).

Accepted for Publication: April 19, 2018.

Published Online: June 27, 2018. doi:10.1001/jamadermatol.2018.1628

Author Contributions: Drs Kreuter and Wieland had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Kreuter and Nasserani contributed equally to this work.

Study concept and design: Kreuter, Wieland.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Kreuter, Nasserani, Wieland.

Critical revision of the manuscript for important intellectual content: Kreuter, Tigges, Oellig, Silling, Akgül, Wieland.

Obtained funding: Wieland.

Administrative, technical, or material support: Nasserani, Tigges, Oellig, Silling, Akgül, Wieland.

Study supervision: Kreuter.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was funded by the German National Reference Center for Papilloma- and Polyomaviruses (German Federal Ministry of Health, grant number 1369-401).

Role of the Funder/Sponsor: The German Federal Ministry of Health had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Monika Junk and Nabila Ristow, both medical technical assistants employed by the University Hospital of Cologne, provided excellent technical assistance. They were not compensated for their contribution.

References
1.
Mirvish  JJ, Pomerantz  RG, Falo  LD  Jr, Geskin  LJ.  Role of infectious agents in cutaneous T-cell lymphoma: facts and controversies.  Clin Dermatol. 2013;31(4):423-431.PubMedGoogle ScholarCrossref
2.
Phan  TG, Dreno  B, da Costa  AC,  et al.  A new protoparvovirus in human fecal samples and cutaneous T cell lymphomas (mycosis fungoides).  Virology. 2016;496:299-305.PubMedGoogle ScholarCrossref
3.
Swerdlow  SH, Campo  E, Pileri  SA,  et al.  The 2016 revision of the World Health Organization classification of lymphoid neoplasms.  Blood. 2016;127(20):2375-2390.PubMedGoogle ScholarCrossref
4.
Herberhold  S, Hellmich  M, Panning  M,  et al.  Human polyomavirus and human papillomavirus prevalence and viral load in non-malignant tonsillar tissue and tonsillar carcinoma.  Med Microbiol Immunol. 2017;206(2):93-103.PubMedGoogle ScholarCrossref
5.
Väisänen  E, Fu  Y, Hedman  K, Söderlund-Venermo  M.  Human protoparvoviruses.  Viruses. 2017;9(11):E354.PubMedGoogle ScholarCrossref
×