Verrucous Carcinoma

Back

Background

Verrucous carcinoma is a relatively uncommon, locally aggressive, clinically exophytic, low-grade, slow-growing, well-differentiated squamous cell carcinoma with minimal metastatic potential.

Verrucous carcinoma may involve the oral cavity, larynx, anogenital region, plantar surface of the foot, and, less commonly, other cutaneous sites. See the image below.



View Image

Verrucous carcinoma; an exophytic and hyperkeratotic mass that discharged malodorous debris through several sinus tracts. Courtesy of J García-Gavín, ....

In 1948, Ackerman first described verrucous carcinoma in the oral cavity as a low-grade tumor that generally is considered a clinicopathologic variant of squamous cell carcinoma.[1] Aird et al first described cutaneous verrucous carcinoma (carcinoma cuniculatum) in 1954, and it was named as such because of its characteristic cryptlike spaces on histology.[2]

Pathophysiology

The pathogenesis of verrucous carcinoma is not yet fully elucidated.[3] Leading theories include human papillomavirus (HPV) infection (oral cavity, anogenital region, plantar foot, and a small subset of cutaneous verrucous carcinoma),[4] chemical carcinogenesis induced by smoking and chewing tobacco,[5] alcohol consumption and betel nut chewing (oral lesions), and chronic inflammation. Schistosomiasis is associated with verrucous carcinoma of the bladder.[6]

Epidemiology

Frequency

The incidence of verrucous carcinoma in the United States and worldwide is unknown.[7]

Race

Verrucous carcinoma is reported predominantly in whites.

Sex

Verrucous carcinoma primarily affects men.

Age

Verrucous carcinoma generally occurs in middle-aged (50s) patients[7] ; however, the anogenital type of verrucous carcinoma has been reported to develop in men aged 18-86 years.[8]

Prognosis

Overall, patients with verrucous carcinoma have a favorable prognosis, although the course of verrucous carcinoma lesions is characterized by slow, continuous, local growth. Morbidity results from local skin and soft-tissue destruction and, occasionally, from perineural, muscle, and even bone invasion. The development of distant metastases is rare. Verrucous carcinoma mortality usually is due to local invasion rather than metastatic spread.

In most cases of verrucous carcinomas, regardless of the variant, the clinical outcome is rarely an aggressive course. Local verrucous carcinoma recurrence following definitive treatment is not uncommon. Regarding oral verrucous carcinoma, the reported recurrence rate ranges from 6-40%. If metastasis does occur, it is mainly at the regional lymph nodes.[9] There have been reports of metastases in distant sites, but this is considered rare. In long-standing lesions, occasional destruction of adjustment structures such as cartilage, tendons, and bones can occur. Patients with oral verrucous carcinoma may be at an increased risk of a second primary oral squamous cell carcinoma, which carries a poor prognosis.

Patient Education

Advise patients about the importance of receiving effective treatment for areas of chronic skin inflammation or trauma (eg, leg or decubitus ulcers) to prevent these problems from developing malignancies within them. Improved oral, genital, and perianal hygiene may help to prevent inflammatory conditions that predispose patients to verrucous carcinoma. Cessation of chewing tobacco use may help to prevent oral verrucous carcinoma.

For patient education resources, see the Cancer and Tumors Center and Warts Center, as well as Skin Cancer, Warts, and Skin Biopsy.

History

Verrucous carcinoma manifests as a cauliflowerlike, exophytic mass that typically develops at sites of chronic irritation and inflammation. Verrucous carcinoma is slow growing, but may display locally aggressive behavior. Penetration into the skin, fascia, and even bone has been reported; however, verrucous carcinoma has low metastatic potential.[10]

Physical

Verrucous carcinoma may affect any part of the skin or mucosa, but it most commonly involves the oral cavity, anogenital region, or sole of the foot. Thus, it has been grouped into four clinicopathologic types based on the affected anatomic site: oroaerodigestive, anogenital, feet, and other cutaneous sites.[8] However, this classification and the associated naming scheme is not used consistently across the literature, leading to confusing and, often, overlapping, nomenclature. Based on the anatomic site of involvement, verrucous carcinoma may be classified as described below.

Oroaerodigestive verrucous carcinoma (Ackerman tumor, oral florid papillomatosis[11] )

The oral cavity is the most common site of occurrence of verrucous carcinoma and represents 2-12% of all oral carcinomas.[9, 12]

Early lesions appear as white, translucent patches on an erythematous base. They may develop in previous areas of leukoplakia, lichen planus,[13, 14] chronic lupus erythematosus, cheilitis, candidiasis, or submucous fibrosis.

The more fully developed lesions are white, soft, cauliflowerlike papillomas with a pebbly surface that may extend and coalesce over large areas of the oral mucosa.

Ulceration, fistulation, and local invasion into soft tissues and bone (eg, mandible) may occur.

Oroaerodigestive verrucous carcinoma most commonly occurs on the buccal mucosa.[9] Other sites of oral involvement are the alveolar ridge, upper and lower gingiva, floor of the mouth, tongue, tonsils, and vermilion border of the lip. Verrucous carcinoma involving the hard palate and upper alveolus is considered more aggressive.[9]

The larynx may also be affected; it usually presents as a bulky exophytic lesion with a papillomatous appearance that projects from the larynx.[15, 16] Furthermore, sinonasal tract involvement has also rarely been reported.[17]

Painful nonmalignant lymphadenopathy can be seen with concurrent infection or inflammation.

Tumors most often grow around the lymph nodes rather than metastasizing to them. If metastases do occur, they usually remain limited to the regional lymph nodes.

Anogenital verrucous carcinoma (Buschke-Löwenstein tumor)

The Buschke-Löwenstein tumor usually manifests as an exophytic tumor of the genital or perianal area, with ulceration and sometimes fistulae and sinuses.[18] The tumor accounts for 5-16% of all penile carcinomas.[19]

They typically manifest as large, exophytic, nonhealing, cauliflowerlike lesions with a verrucous or ulcerated surface. The Buschke-Löwenstein tumor usually can only be differentiated from ordinary condylomata based on histologic findings. These tumors tend to infiltrate deeply, and recurrence is common.[18, 20]

The Buschke-Löwenstein tumor is preferentially seen in men and immunocompromised patients.[18] It commonly occurs on the glans penis, mainly in uncircumcised men. In females, this tumor is most often found on the vulva.[21]

Less commonly, the Buschke-Löwenstein tumor occurs in the bladder[6, 22] or on vaginal, cervical, perianal, scrotal, and pelvic organs.

Verrucous carcinoma of the foot (epithelioma cuniculatum)[8, 23, 24]

Verrucous carcinoma of the skin is typically a long-standing, slow-growing tumor that is usually found at the sole of the foot and, less frequently, the toes or heels.[25]

Lesions are usually slow growing, exophytic, and locally invasive. Lesions may exhibit hyperkeratosis, ulceration, and sinuses that may drain foul-smelling discharge and cause pain, bleeding, and difficulty walking.

Lesions can often be misdiagnosed for plantar warts that grow slowly into a large exophytic mass.[24]

Verrucous carcinoma of the foot most often occurs as a single mass or plaque, but multiple verrucous carcinomas on the feet and ankles have been reported.[25]

Verrucous carcinoma of the foot is considered to have a very low incidence of metastases. Nevertheless, in long-standing tumors, underlying structures such as the bone, cartilage, and tendons can be involved.[24]

Other cutaneous sites (cutaneous verrucous carcinoma)[4, 8, 24]

Verrucous carcinomas arising from other cutaneous sites beyond the foot (eg, scalp, face, nail apparatus, arm) have also been reported.[26, 24, 27, 28]

These tumors, like their counterparts encountered on the sole of the foot, tend to present as slowly enlarging, locally aggressive, exophytic masses with low metastatic potential.

Cutaneous verrucous carcinoma has been reported to develop at sites of inflammation or scarring such as decubitus ulcers, gunshot wounds, burn scars, lupus vulgaris scars, and areas affected by hidradenitis suppurativa.[8, 29]

Causes

HPV may play a role in the development of verrucous carcinoma. HPV types 6 and 11 are most frequently associated with the Buschke-Löwenstein tumor.[8] In plantar lesions, HPV type 16 has been reported.[30] Finally, HPV type 33 has been reported in a verrucous carcinoma of the scalp.[4]

Despite the presence of HPV strains within some lesions of verrucous carcinoma, a causal relationship has not been proven and remains controversial.[31, 32]

Inflammation appears to sometimes play a role in the development of verrucous carcinoma. For instance, cutaneous verrucous carcinoma may develop at sites of inflammation or scarring such as decubitus ulcers or areas affected by hidradenitis suppurativa.[8, 29] In addition, lichen sclerosus may predispose patients to the development of penile verrucous carcinomas.[33] Similarly, verrucous carcinomas of the oral cavity have been reported to develop in patients with long-standing oral ulcerative lichen planus and chronic candidiasis.

Associations in oral verrucous carcinoma have been found in patients who chewed or inhaled tobacco and betel nuts, dipped snuff, and/or consumed alcohol. Lesions developed at the sites where tobacco was habitually placed in the mouth.[9]

Furthermore, oral verrucous carcinoma is associated with poor dental hygiene, ill-fitting dentures, and low socioeconomic status. Oral verrucous carcinoma has a higher incidence in males and in immunocompromised patients.[9]

Schistosomal infection often is coexistent with verrucous carcinoma of the bladder.[6]

Imaging Studies

Computed tomography or magnetic resonance imaging may be used to demonstrate the exact location and extent of the verrucous carcinoma for preoperative staging and surgical planning.

Procedures

A skin biopsy is always required for definitive diagnosis of verrucous carcinoma, despite the fact that the diagnosis is suspected strongly on clinical grounds.

Biopsy is performed routinely in the physician's office using a local anesthetic.

All skin biopsy specimens obtained to diagnose verrucous carcinoma must reach at least the depth of the mid dermis to allow for determination of the presence or absence of invasive disease.

A deep (scoop) shave biopsy, a punch biopsy, an incisional biopsy, or an excisional biopsy may be performed.

Pathology readings preferably are made by a dermatopathologist who has extensive experience with verrucous carcinoma.

Histologic Findings

Regardless of site of origin, verrucous carcinomas share the same histological features. Verrucous carcinoma of all types may resemble a verruca superficially, with hyperkeratosis, parakeratosis, acanthosis, papillomatosis, and granular cell layer vacuolization. A characteristic feature is the blunt projections of well-differentiated epithelium surrounded by edematous stroma and chronic inflammatory cells that extend into the dermis, sometimes forming sinuses filled with keratin. Cutaneous verrucous carcinomas may be confused with warty carcinomas, but the higher-grade cytological atypia and the more infiltrative growth pattern of warty carcinomas can help to differentiate.

Staging

Although most verrucous carcinomas are nonmetastatic, staging is still based on the tumor, nodes, metastases (TNM) staging system. The specifics of staging vary based on the anatomic site, with slightly different criteria for oral, anal, and penile lesions. No specific staging system exists for cutaneous verrucous carcinoma; however, the seventh edition of the American Joint Committee for Cancer Staging Manual does propose a staging system for cutaneous squamous cell carcinomas and other cutaneous carcinomas, as follows[34] :

Surgical Care

Most physicians treat patients with cutaneous verrucous carcinoma in their offices. Complete tumor removal should be performed expeditiously because verrucous carcinoma can recur, metastasize, and, ultimately, cause death.[35] Recurrent verrucous carcinoma carries a relatively poor prognosis.

Surgical excision and Mohs micrographic (MMS) surgery represent the treatments of choice for cutaneous verrucous carcinomas.[36, 37]

Surgical excision [38]

Complete surgical resection with clear margins is recommended once the diagnosis of verrucous carcinoma has been established.

Standard excision with permanent conventional sections is a highly effective treatment for many verrucous carcinomas. The depth of the excision should include the subcutaneous fat because even small verrucous carcinomas may extend into the subcutaneous fat.

The disadvantages of excision with an arbitrary margin are that in some cases, the pathology reveals a subclinical positive margin, requiring further surgery. In extensive tumors with inflammatory changes, the surgical margin may be difficult to define. Furthermore, incomplete surgical resection can lead to acceleration in the growth of the tumor. Finally, as opposed to tissue-sparing modalities, more healthy tissue may be excised than is necessary.[9]

Mohs surgery [39, 40, 41]

A dermatologic surgeon usually offers MMS. The main advantage of MMS over simple excision in the extirpation of cutaneous verrucous carcinoma is the ability to examine all excision margins (deep and lateral) and to carefully map residual foci of invasive carcinoma.

MMS allows for tissue preservation, thus facilitating reconstruction; this can be of particular benefit in sensitive areas of the body such as the anogenital region where preservation of sexual function and body image are of great importance.

MMS is performed routinely in an outpatient setting with the patient under local anesthesia.

MMS is not widely available outside the United States.

A multidisciplinary approach using MMS performed in conjunction with a plastic surgeon, otolaryngologist, and radiation oncologist may allow for the complete removal of deeply invasive verrucous carcinoma, preservation of vital structures, and facilitation of the reconstruction of a large operative defect.

Because of its many advantages, MMS is the procedure of choice for verrucous carcinoma for which tissue preservation is needed. Furthermore, surgery for verrucous carcinoma using MMS may be an integral component in the management of certain verrucous carcinomas that otherwise would be beyond the experience of the cutaneous surgeon.

Cryosurgery [42, 43]

Cryosurgery using liquid nitrogen is a safe and low-cost procedure for the ablation of selected verrucous carcinomas and is well tolerated by patients.

The major disadvantage of cryosurgery is the lack of histologic control and lack of precision in application of treatment, which often leads to the need for multiple treatments. Initial shave excision of the bulk of the tumor may allow for more direct therapy and thus, a higher cure rate.

This procedure is the least likely to result in cure and, therefore, is not a preferred intervention.

Radiation therapy [44, 45, 46]

Radiation therapy offers the potential advantage of avoiding the trauma and deformity of a surgical procedure, but it remains a controversial modality, owing to its potential association with transformation to a high-grade squamous carcinoma. Although reported in earlier literature,[47] the association between radiation and anaplastic transformation of verrucous carcinoma appears to be less frequent than previously reported.[48, 49]

Ionizing radiation therapy is used mainly as a treatment for primary cutaneous carcinoma in patients who cannot tolerate surgery (eg, elderly patients).

Although the initial cosmetic result following radiation often is good, the long-term result frequently is poor, with atrophy, hypopigmentation, and telangiectasia. Some patients treated with radiation also develop radiation necrosis. This risk increases over time.

Radiation therapy is not advocated for use over bony structures because of the risk of osteoradionecrosis. Radiation therapy is not advocated for patients who are young or middle aged.

Radiation therapy is expensive and requires multiple visits. The procedure is blind to histologic margin control and may be linked to anaplastic transformation. For these reasons, the use of radiation as primary therapy for verrucous carcinoma generally is restricted to older patients who cannot tolerate or who refuse surgery.

Other considerations

Other treatments that have been used for cutaneous verrucous carcinomas with variable success include curettage and electrodessication, topical or systemic chemotherapy (bleomycin, 5-fluorouracil, cisplatin, methotrexate), carbon dioxide laser, intralesional interferon-alfa, imiquimod, and photodynamic therapy.[50]

Possible medicolegal pitfalls

The main pitfall in the diagnostic evaluation is taking an inadequate biopsy specimen, leading some to advise the use of excisional biopsy whenever the diagnosis of verrucous carcinoma is suspected.[38] Additionally, in some cases, the carcinoma is so well differentiated that the pathologist may read the tissue as pseudoepitheliomatous hyperplasia. Verrucous carcinoma has the potential to cause substantial morbidity and even mortality, and physicians who diagnose and treat verrucous carcinoma are held legally accountable for their actions.

Failure to ensure adequate patient follow-up care is a pitfall because primary treatment of verrucous carcinoma is not a guarantee of cure. Not informing patients of the potential morbidity associated with verrucous carcinoma may lead to the lesion being regarded as trivial and not requiring follow-up care. The courts hold the physician, not the patient, responsible for appropriate follow-up care. Missed appointments for patients with verrucous carcinoma before or following surgery may indicate a worried or angry patient and should be followed up with a phone call to reschedule and, if necessary, with a certified letter.

Failure to outline all possible risks prior to verrucous carcinoma surgery is another pitfall. Surgery for patients with verrucous carcinoma may cause bleeding, infection, scar formation, deformity, and nerve damage. Removal of deeply invasive lesions may lead to substantial morbidity, including pain syndromes and paralysis. If a surgical complication develops, the physician who performed the primary procedure is held legally responsible, regardless of who handles the complication. Any patient with lesions that are outside the realm of comfort of an individual physician should be referred to another physician.

Long-Term Monitoring

Verrucous carcinoma usually is cured with appropriate therapy. However, recurrence of cutaneous carcinoma with clear surgical margins has been reported. In addition, patients with a history of verrucous carcinoma should be evaluated with regular skin examinations at 3- to 12-month intervals.

Author

Jennifer Shuley Ruth, MD, Resident Physician, Department of Dermatology, Baylor College of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Mohsin R Mir, MD, Director, High Risk Skin Cancer Clinic, Assistant Professor, Mohs Surgery, Laser and Cosmetic Surgery, Department of Dermatology, Baylor College of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Disclosure: Nothing to disclose.

John G Albertini, MD, Private Practice, The Skin Surgery Center; Clinical Associate Professor (Volunteer), Department of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine; President-Elect, American College of Mohs Surgery

Disclosure: Received grant/research funds from Genentech for investigator.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: nakedbiome<br/>Received income in an amount equal to or greater than $250 from: elsevier;webMD<br/>editor in chief for: statpearls.

Additional Contributors

Kelly M Cordoro, MD, Assistant Professor of Clinical Dermatology and Pediatrics, Department of Dermatology, University of California, San Francisco School of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Mohsin Ali, MBBS, FRCP, MRCP, MRCPI, Consulting Staff, Department of Dermatology, Amersham General Hospital, UK

Disclosure: Nothing to disclose.

Sohail Mansoor, MBBS, MSc Dermatologist and Lead Physician in Dermatologic Surgery, Department of Dermatology, Barnet Hospital, UK

Sohail Mansoor, MBBS, MSc is a member of the following medical societies: American Academy of Anti-Aging Medicine, American Academy of Dermatology, American Society for Dermatologic Surgery, Royal College of Physicians and Surgeons of Glasgow, and Royal College of Physicians of the United Kingdom

Disclosure: Nothing to disclose.

Nicole Sakka, MBBS Foundation Year 2, Royal Liverpool and Broadgreen University Hospital, Liverpool, UK

Disclosure: Nothing to disclose.

Bassam Zeina, MD, PhD Consulting Staff, Department of Dermatology, Milton Keynes Hospital, UK

Bassam Zeina, MD, PhD is a member of the following medical societies: British Association of Dermatologists, British Medical Association, and Royal Society of Medicine

Disclosure: Nothing to disclose.

References

  1. Ackerman LV. Verrucous carcinoma of the oral cavity. Surgery. 1948 Apr. 23(4):670-8. [View Abstract]
  2. Aird I, Johnson HD, Lennox B, Stansfeld AG. Epithelioma cuniculatum: a variety of squamous carcinoma peculiar to the foot. Br J Surg. 1954 Nov. 42(173):245-50. [View Abstract]
  3. Wang YH, Tian X, Liu OS, Fang XD, Quan HZ, Xie S, et al. Gene profiling analysis for patients with oral verrucous carcinoma and oral squamous cell carcinoma. Int J Clin Exp Med. 2014. 7(7):1845-52. [View Abstract]
  4. Murao K, Kubo Y, Fukumoto D, Matsumoto K, Arase S. Verrucous carcinoma of the scalp associated with human papillomavirus type 33. Dermatol Surg. 2005 Oct. 31(10):1363-5. [View Abstract]
  5. Mirbod SM, Ahing SI. Tobacco-associated lesions of the oral cavity: Part II. Malignant lesions. J Can Dent Assoc. 2000 Jun. 66(6):308-11. [View Abstract]
  6. Blackmore CC, Ratcliffe NR, Harris RD. Verrucous carcinoma of the bladder. Abdom Imaging. 1995 Sep-Oct. 20(5):480-2. [View Abstract]
  7. Terada T. Verrucous carcinoma of the skin: a report on 5 Japanese cases. Ann Diagn Pathol. 2011 Jun. 15(3):175-80. [View Abstract]
  8. Schwartz RA. Verrucous carcinoma of the skin and mucosa. J Am Acad Dermatol. 1995 Jan. 32(1):1-21. [View Abstract]
  9. Walvekar RR, Chaukar DA, Deshpande MS, et al. Verrucous carcinoma of the oral cavity: A clinical and pathological study of 101 cases. Oral Oncol. 2009 Jan. 45(1):47-51. [View Abstract]
  10. Hagiwara H, Kanazawa T, Ishikawa K, et al. Invasive verrucous carcinoma: a temporal bone histopathology report. Auris Nasus Larynx. 2000 Apr. 27(2):179-83. [View Abstract]
  11. Grinspan D, Abulafia J. Oral florid papillomatosis (verrucous carcinoma). Int J Dermatol. 1979 Oct. 18(8):608-22. [View Abstract]
  12. Depprich RA, Handschel JG, Fritzemeier CU, Engers R, Kubler NR. Hybrid verrucous carcinoma of the oral cavity: A challenge for the clinician and the pathologist. Oral Oncology EXTRA. 2006. 42:85-90.
  13. Castano E, Lopez-Rios F, Alvarez-Fernandez JG, Rodriguez-Peralto JL, Iglesias L. Verrucous carcinoma in association with hypertrophic lichen planus. Clin Exp Dermatol. 1997 Jan. 22(1):23-5. [View Abstract]
  14. Warshaw EM, Templeton SF, Washington CV. Verrucous carcinoma occurring in a lesion of oral lichen planus. Cutis. 2000 Apr. 65(4):219-22. [View Abstract]
  15. Huang SH, Lockwood G, Irish J, et al. Truths and myths about radiotherapy for verrucous carcinoma of larynx. Int J Radiat Oncol Biol Phys. 2009 Mar 15. 73(4):1110-5. [View Abstract]
  16. Witt RL, Wilson P. Missed opportunity for larynx preservation? Failure to distinguish verrucous and squamous cell carcinoma on microlaryngoscopy and biopsy. J Voice. 2009 Jan. 23(1):140-2. [View Abstract]
  17. Shiomori T, Udaka T, Nagatani G, et al. Association of verrucous carcinoma and inverted papilloma in the sinonasal tract. Auris Nasus Larynx. 2007 Jun. 34(2):281-5. [View Abstract]
  18. Levy A, Lebbe C. [Buschke-Löwenstein tumour: diagnosis and treatment]. Ann Urol (Paris). 2006 Jun. 40(3):175-8. [View Abstract]
  19. Nomikos M, Barmpoutis P, Papakonstantinou E, et al. A giant verrucous carcinoma of the penis presenting with urinary sepsis and angina. Case Rep Med. November 12, 2014. 2014:[View Abstract]
  20. Shenoy S. Perianal giant condyloma acuminatum (Buschke-Löwenstein tumor). Skinmed. 2014 Mar-Apr. 12(2):114-5. [View Abstract]
  21. Sandhu R, Min Z, Bhanot N. A gigantic anogenital lesion: Buschke-lowenstein tumor. Case Rep Dermatol Med. November 6, 2014. 2014:[View Abstract]
  22. Groeneveld AE. Verrucous carcinoma of the bladder. Br J Urol. 1992 Jul. 70(1):96-7. [View Abstract]
  23. Ho J, Diven DG, Butler PJ, Tyring SK. An ulcerating verrucous plaque on the foot. Verrucous carcinoma (epithelioma cuniculatum). Arch Dermatol. 2000 Apr. 136(4):547-8, 550-1. [View Abstract]
  24. Vandeweyer E, Sales F, Deraemaecker R. Cutaneous verrucous carcinoma. Br J Plast Surg. 2001 Mar. 54(2):168-70. [View Abstract]
  25. Kuan YZ, Hsu HC, Kuo TT, Huang YH, Ho HC. Multiple verrucous carcinomas treated with acitretin. J Am Acad Dermatol. 2007 Feb. 56(2 Suppl):S29-32. [View Abstract]
  26. Pattee SF, Bordeaux J, Mahalingam M, Nitzan YB, Maloney ME. Verrucous carcinoma of the scalp. J Am Acad Dermatol. 2007 Mar. 56(3):506-7. [View Abstract]
  27. Sheen MC, Sheen YS, Sheu HM, Wong TW, Lee YY, Wu CF, et al. Subungual verrucous carcinoma of the thumb treated by intra-arterial infusion with methotrexate. Dermatol Surg. 2005 Jul. 31(7 Pt 1):787-9. [View Abstract]
  28. Bernadas SR, Evgenios E, Dimitriadis PA, Hamal P, Uppal R. Verrucous carcinoma of the upper arm. ANZ J Surg. 2014 Dec. 84(12):983-4. [View Abstract]
  29. Cosman BC, O'Grady TC, Pekarske S. Verrucous carcinoma arising in hidradenitis suppurativa. Int J Colorectal Dis. 2000 Nov. 15(5-6):342-6. [View Abstract]
  30. Schell BJ, Rosen T, Rady P, et al. Verrucous carcinoma of the foot associated with human papillomavirus type 16. J Am Acad Dermatol. 2001 Jul. 45(1):49-55. [View Abstract]
  31. Patel KR, Chernock RD, Zhang TR, Wang X, El-Mofty SK, Lewis JS Jr. Verrucous carcinomas of the head and neck, including those with associated squamous cell carcinoma, lack transcriptionally active high-risk human papillomavirus. Hum Pathol. 2013 Nov. 44(11):2385-92. [View Abstract]
  32. Odar K, Kocjan BJ, Hošnjak L, Gale N, Poljak M, Zidar N. Verrucous carcinoma of the head and neck - not a human papillomavirus-related tumour?. J Cell Mol Med. 2014 Apr. 18(4):635-45. [View Abstract]
  33. Nasca MR, Innocenzi D, Micali G. Penile cancer among patients with genital lichen sclerosus. J Am Acad Dermatol. 1999 Dec. 41(6):911-4. [View Abstract]
  34. Warner CL, Cockerell CJ. The new seventh edition American Joint Committee on Cancer staging of cutaneous non-melanoma skin cancer: a critical review. Am J Clin Dermatol. 2011 Jun 1. 12(3):147-54. [View Abstract]
  35. Spyriounis PK, Tentis D, Sparveri IF, Arvanitis T. Plantar epithelioma cuniculatum. A case report with review of the literature. European Journal of Plastic Surgery. October 2004. 27(5):253-6.
  36. Abbas MA. Wide local excision for Buschke-Löwenstein tumor or circumferential carcinoma in situ. Tech Coloproctol. 2011 Sep. 15(3):313-8. [View Abstract]
  37. Sciubba JJ, Helman JI. Current management strategies for verrucous hyperkeratosis and verrucous carcinoma. Oral Maxillofac Surg Clin North Am. 2013 Feb. 25(1):77-82, vi. [View Abstract]
  38. Koch H, Kowatsch E, Hödl S, Smola MG, Radl R, Hofmann T, et al. Verrucous carcinoma of the skin: long-term follow-up results following surgical therapy. Dermatol Surg. 2004 Aug. 30(8):1124-1130. [View Abstract]
  39. Alkalay R, Alcalay J, Shiri J. Plantar verrucous carcinoma treated with Mohs micrographic surgery: a case report and literature review. J Drugs Dermatol. 2006 Jan. 5(1):68-73. [View Abstract]
  40. Padilla RS, Bailin PL, Howard WR, Dinner MI. Verrucous carcinoma of the skin and its management by Mohs' surgery. Plast Reconstr Surg. 1984 Mar. 73(3):442-7. [View Abstract]
  41. Casado-Verrier B, Feltes-Ochoa R, Gómez-Fernández C, Feito-Rodríguez M, Beato-Merino M, Alonso-Pacheco ML. Mohs micrographic surgery for verrucous carcinoma of the anogenital area: report of two cases. Int J Dermatol. 2012 Jun. 51(6):722-5. [View Abstract]
  42. Ishida CE, Ramos-e-Silva M. Cryosurgery in oral lesions. Int J Dermatol. 1998 Apr. 37(4):283-5. [View Abstract]
  43. Yeh CJ. Treatment of verrucous hyperplasia and verrucous carcinoma by shave excision and simple cryosurgery. Int J Oral Maxillofac Surg. 2003 Jun. 32(3):280-3. [View Abstract]
  44. Ferlito A, Rinaldo A, Mannara GM. Is primary radiotherapy an appropriate option for the treatment of verrucous carcinoma of the head and neck?. J Laryngol Otol. 1998 Feb. 112(2):132-9. [View Abstract]
  45. Foroudi F, Turner S. Verrucous scrotal carcinoma: a radioresponsive tumor. J Urol. 1999 Nov. 162(5):1694-5. [View Abstract]
  46. Schwade JG, Wara WM, Dedo HH, Phillips TL. Radiotherapy for verrucous carcinoma. Radiology. 1976 Sep. 120(3):677-9. [View Abstract]
  47. Perez CA, Kraus FT, Evans JC, Powers WE. Anaplastic transformation in verrucous carcinoma of the oral cavity after radiation therapy. Radiology. 1966 Jan. 86(1):108-115. [View Abstract]
  48. Ferlito A, Rinaldo A, Mannarà GM. Is primary radiotherapy an appropriate option for the treatment of verrucous carcinoma of the head and neck?. J Laryngol Otol. 1998 Feb. 112(2):132-9. [View Abstract]
  49. Huang SH, Lockwood G, Irish J, Ringash J, Cummings B, Waldron J. Truths and myths about radiotherapy for verrucous carcinoma of larynx. Int J Radiat Oncol Biol Phys. 2009 Mar 15. 73(4):1110-5. [View Abstract]
  50. Nikkels AF, Thirion L, Quatresooz P, Piérard GE. Photodynamic therapy for cutaneous verrucous carcinoma. J Am Acad Dermatol. 2007 Sep. 57(3):516-9. [View Abstract]

Verrucous carcinoma; an exophytic and hyperkeratotic mass that discharged malodorous debris through several sinus tracts. Courtesy of J García-Gavín, D González-Vilas, L Rodríguez-Pazos, D Sánchez-Aguilar, and J Toribio, via Wikimedia Commons.

Verrucous carcinoma; an exophytic and hyperkeratotic mass that discharged malodorous debris through several sinus tracts. Courtesy of J García-Gavín, D González-Vilas, L Rodríguez-Pazos, D Sánchez-Aguilar, and J Toribio, via Wikimedia Commons.