Case Report

Coincidental Consort Clear Cell Cutaneous Carcinom: Facial Squamous Cell Carcinoma In Situ Containing Human Papillomavirus and Cancer Cells with Clear Cytoplasm in an Octogenarian Couple

Authors: Philip R. Cohen, MD, Keith E. Schulze, MD, Peter L. Rady, MD, PhD, Stephen K. Tyring, MD, PhD, MBA, Qin He, MD, Paul T. Martinelli, MD, Bruce R. Nelson, MD

Abstract

Clear cell squamous cell carcinoma in situ, also referred to as pagetoid or clear cell Bowen disease, is a rare pathologic variant of this neoplasm. It is characterized by neoplastic cells with clear or pale cytoplasm. An octogenarian husband and wife concurrently developed new facial skin lesions which demonstrated squamous cell carcinoma in situ consisting of cancer cells with clear cytoplasm. Cutaneous human papillomavirus (HPV) typing detected HPV Type 5 and HPV Type 21 in the tumors of the husband and wife, respectively. HPV is a potential etiologic factor in the oncogenesis of nonmelanoma skin cancer, and HPV DNA has been demonstrated in extragenital squamous cell carcinoma in situ. The detection of DNA from different HPV types in the tumors of our patients suggests that the concurrent occurrence of their skin cancers may have been coincidental. However, the presence of HPV DNA in their tumors introduces the possibility of a viral-associated oncogenesis for clear cell squamous cell carcinoma in situ.


Key Points


* Clear cell squamous cell carcinoma in situ, characterized by neoplastic cells with clear or pale cytoplasm, is a rare pathologic variant of this neoplasm.


* The pathologic differential diagnosis of clear cell squamous cell carcinoma in situ includes extramammary Paget disease, mammary Paget disease, benign and malignant tumors characterized by intraepidermal pagetoid cells, and other clear cell neoplasms of the skin.


* Human papillomavirus is a potential etiologic factor in the oncogenesis of nonmelanoma skin cancer.


* Human papillomavirus DNA has been demonstrated in extragenital squamous cell carcinoma in situ.


* The detection of HPV DNA in our patients’ clear cell squamous cell carcinomas in situ introduces the possibility that a viral-associated oncogenesis may contribute to the development of this pathologic variant of skin cancer.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Arlette JP, Trotter MJ. Squamous cell carcinoma in situ of the skin: history, presentation, biology and treatment. Australas J Dermatol 2004;45:1–11.
 
2. Cassarino DS, DeRienzo DP, Barr RJ. Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification. Part one. J Cutan Pathol 2006;33:191–206.
 
3. Cassarino DS, DeRienzo DP, Barr RJ. Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification: part two. J Cutan Pathol 2006;33:261–279.
 
4. Strayer DS, Santa Cruz DJ. Carcinoma in situ of the skin: a review of histopathology. J Cutan Pathol 1980;7:244–259.
 
5. Suster S. Clear cell tumors of the skin. Semin Diagn Pathol 1996;13:40–59.
 
6. Rosen L, Amazon K, Frank B. Bowen’s disease, Paget’s disease, and malignant melanoma in situ. South Med J 1986;79:410–413.
 
7. Kwon TJ, Ro JY, MacKay B. Clear cell carcinoma: an ultrastructural study of 57 tumors from various sites. Ultrastruct Pathol 1996;20:519–527.
 
8. Cruces M, Losada A, de la Torre C, et al. Clear cell squamous cell carcinoma [abstract].Am J Dermatopathol 1996;18:438.
 
9. Kuo T. Clear cell carcinoma of the skin: a variant of the squamous cell carcinoma that simulates sebaceous carcinoma. Am J Surg Pathol 1980;4:573–583.
 
10. McKinley E, Valles R, Bang R, et al. Signet-ring squamous cell carcinoma: a case report. J Cutan Pathol 1998;25:176–181.
 
11. Cramer SF, Heggeness LM. Signet-ring squamous cell carcinoma. Am J Clin Pathol 1989;91:488–491.
 
12. Requena L, Sanchez M, Requena I, et al. Clear cell squamous cell carcinoma: a histologic, immunohistologic, and ultrastructural study. J Dermatol Surg Oncol 1991;17:656–660.
 
13. Williamson JD, Colome MI, Sahin A, et al. Pagetoid Bowen disease: a report of 2 cases that express cytokeratin 7. Arch Pathol Lab Med 2000;124:427–430.
 
14. Kohler S, Rouse RV, Smoller BR. The differential diagnosis of Pagetoid cells in the epidermis. Mod Pathol 1998;11:79–92.
 
15. Raiten K, Paniago-Pereira C, Ackerman AB. Pagetoid Bowen’s disease vs extramammary Paget’s disease. J Dermatol Surg 1976;2:24–25.
 
16. Hernandez-Perez E, Figueroa DE. Warty and clear cell Bowen’s disease. Int J Dermatol 2005;44:586–587.
 
17. Fitzpatrick JE. The histologic diagnosis of intraepithelial Pagetoid neoplasms. Clin Dermatol 1991;9:255–259.
 
18. Forslund O, Ly H, Higgins G. Improved detection of cutaneous human papillomavirus DNA by single tube nested ‘hanging droplet’ PCR. J Virol Methods 2003;110:129–136.
 
19. de Oliveira WR, He Q, Rady PL, et al. HPV typing in Brazilian patients with epidermodysplasia verruciformis: high prevalence of EV-HPV 25. J Cutan Med Surg 2004;8:110–115.
 
20. Tatemoto Y, Saka M, Tanimura T, et al. Immunohistochemical observations on binding of monoclonal antibody to epithelial membrane antigen in epithelial tumors of the oral cavity and skin. Oral Surg Oral Med Oral Pathol 1987;64:721–726.
 
21. Civatte J. Clear-cell tumors of the skin: a histopathologic review. J Cutan Pathol 1984;11:165–175.
 
22. Pfistser H. Chapter 8: human papillomavirus and skin cancer. J Natl Cancer Inst Monogr 2003;31:52–56.
 
23. Bouwes Bavinck JN, Feltkamp M, Struijk L, et al. Human papillomavirus infection and skin cancer risk in organ transplant recipients. J Investig Dermatol Symp Proc 2001;6:207–211.
 
24. Iftner A, Klug SJ, Garbe C, et al. The prevalence of human papillomavirus genotypes in nonmelanoma skin cancers of nonimmunosuppressed individuals identifies high-risk genital types as possible risk factors. Cancer Res 2003;63:7515–7519.
 
25. Harwood CA, Proby CM. Human papillomaviruses and non-melanoma skin cancer. Curr Opin Infect Dis 2002;15:101–114.
 
26. Quereux G, N′Guyen JM, Dreno B. Human papillomavirus and extragenital in situ carcinoma. Dermatology 2004;209:40–45.
 
27. Masini C, Fuchs PG, Gabrielli F, et al. Evidence for the association of human papillomavirus infection and cutaneous squamous cell carcinoma in immunocompetent individuals. Arch Dermatol 2003;139:890–894.
 
28. Alam M, Cladwell JB, Eliezri YD. Human papillomavirus-associated digital squamous cell carcinoma: literature review and report of 21 new cases. J Am Acad Dermatol 2003;48:385–393.
 
29. High WA, Tyring SK, Taylor RS. Rapidly enlarging growth of the proximal nail fold. Dermatol Surg 2003;29:984–986.
 
30. Sra KK, Torres G, Rady P, et al. Molecular diagnosis of infectious diseases in dermatology. J Am Acad Dermatol 2005;53:749–765.
 
31. Gravitt PE, Peyton CL, Alessi TQ, et al. Improved amplification to genital human papillomaviruses. J Clin Microbiol 2000;38:357–361.
 
32. van den Brule AJ, Pol R, Fransen-Daalmeijer N, et al. GP5+/6+ PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes. J Clin Microbiol 2002;40:779–787.
 
33. Berkhout RJ, Tieben LM, Smits HL, et al. Nested PCR approach for detection and typing of epidermodysplasia verruciformis-associated human papillomavirus types in cutaneous cancers from renal transplant recipients. J Clin Microbiol 1995;33:690–695.
 
34. Meyer T, Arndt R, Christophers E, et al. Frequency and spectrum of HPV types detected in cutaneous squamous-cell carcinomas depend on the HPV detection system: a comparison of four PCR assays. Dermatology 2000;201:204–211.
 
35. Fuessel Haws AL, He Q, Rady PL, et al. Nested PCR with the PGMY09/11 and GP5+/6+ primer sets improves detection of HPV DNA in cervical samples. J Virol Methods 2004;122:87–93.
 
36. Forslund O, DeAngelis PM, Beigi M, et al. Identification of human papillomavirus in keratoacanthomas. J Cutan Pathol 2003;30:423–429.
 
37. Harwood CA, Spink PJ, Surentheran T, et al. Detection of human papillomavirus DNA in PUVA-associated non-melanoma skin cancers. J Invest Dermatol 1998;111:123–127.
 
38. Mahe E, Bodemer C, Descamps V, et al. High frequency of detection of human papillomaviruses associated with epidermodysplasia verruciformis in children with psoriasis. Br J Dermatol 2003;149:819–825.