Verrucous Carcinoma: Symptoms, Types, Causes and Treatment

Verrucous carcinoma is a rare, slow-growing variant of squamous cell carcinoma that can present unique challenges in diagnosis and management. Although it behaves in a relatively indolent manner compared to other cancers, its local aggressiveness and tendency for recurrence demand close attention from both clinicians and patients. This article explores the key aspects of verrucous carcinoma—its symptoms, types, causes, and modern treatment strategies—drawing from the latest research and clinical case reports.

Symptoms of Verrucous Carcinoma

Recognizing the symptoms of verrucous carcinoma early is crucial, as its slow progression and often subtle presentation can lead to diagnostic delays. Patients may not initially realize the seriousness of their condition, as the tumor often masquerades as benign or inflammatory lesions.

Symptom	Area Affected	Onset & Duration	Source(s)
Dysphagia	Esophagus	Gradual, months to years	1 3 4
Weight loss	General	Progressive, over months	1 3 4
Non-healing lesion	Skin/oral/genital	Persistent, slow-growing	6 9 10
Itching	Vulva/skin	Chronic	2 6
Tumor mass	Any site	Exophytic, enlarging	2 6 8 9
Ulceration	Skin/extremities	Chronic or recurrent	6 9
Local pain/soreness	Oral cavity, skin	Mild to moderate	10

Table 1: Key Symptoms

Understanding the Clinical Presentation

Verrucous carcinoma most commonly presents as a slow-growing, wart-like mass that may persist for months or even years before diagnosis. Its indolent appearance can result in misdiagnosis as benign lesions or chronic inflammatory conditions such as candidiasis or leukoplakia, especially in the esophagus and oral cavity 1 3 10.

Symptom Breakdown by Body Site

• Esophagus: Dysphagia (difficulty swallowing) is the most common symptom, often accompanied by significant weight loss. The tumor can be misdiagnosed as chronic infection or inflammation, leading to malnutrition and poor surgical outcomes if not caught early 1 3 4.
• Oral Cavity: Presents as persistent white or nodular plaques, often painless but may cause soreness or discomfort. Longstanding non-healing lesions in smokers or those with alcohol use are suspicious 10 13.
• Skin and Extremities: Non-healing ulcers or wart-like growths, sometimes with central ulceration, especially in areas of chronic irritation or trauma (e.g., heel, lower leg, buttock, fingers). Itching and local pain are possible 6 9.
• Genital and Vulvar Regions: May present as large, exophytic, sometimes itchy tumors that can be mistaken for benign growths or chronic infections 2 8.

Challenges in Diagnosis

The slow and locally invasive nature of verrucous carcinoma, coupled with its non-specific symptoms, often leads to delays in diagnosis. Biopsy and histopathological examination are essential for definitive diagnosis, as clinical features alone can be misleading 2 6 10.

Types of Verrucous Carcinoma

Verrucous carcinoma can manifest in several anatomical forms, each with unique clinical features but sharing a common histopathological profile. Understanding these types aids in accurate diagnosis and tailored management.

Type/Name	Typical Site	Notable Features	Source(s)
Oral florid papillomatosis	Oral mucosa	Exophytic, warty lesions	5 8 13
Epithelioma cuniculatum	Plantar foot, digits	Deeply invasive, ulcerated	5 8 9
Buschke-Löwenstein tumor	Genito-gluteal	Large, cauliflower-like	5 8 12
Papillomatosis cutis carcinoides	Skin	Wart-like, chronic sites	5 6 8
Verrucous esophageal carcinoma	Esophagus	Superficial, polypoid	1 3 4
Vulvar/vaginal VC	Vulva, vagina	Large, exophytic masses	2 8

Table 2: Major Types of Verrucous Carcinoma

Anatomical Variants

Verrucous carcinoma has been classified based on its anatomical site:

• Oral Florid Papillomatosis (Oral VC): Originally described by Ackerman, this form appears as a proliferative, wart-like lesion in the oral cavity—most commonly on the buccal mucosa, gingiva, or tongue. It is often mistaken for benign hyperplasia or leukoplakia 5 8 13.
• Epithelioma Cuniculatum: Most frequently seen on the plantar surface of the foot or digits, this type can invade deeply into soft tissue and bone, occasionally requiring amputation 5 8 9.
• Buschke-Löwenstein Tumor: Predominantly affects the anogenital region, presenting as massive, cauliflower-like growths that can destroy adjacent tissues if left untreated 5 8 12.
• Papillomatosis Cutis Carcinoides: Involves the skin, particularly in areas subject to chronic inflammation or irritation, such as the buttocks or lower extremities 5 6 8.
• Esophageal Verrucous Carcinoma: A rare subtype of esophageal squamous cell carcinoma, typically presenting as a slow-growing, exophytic mass causing dysphagia 1 3 4.
• Vulvar and Vaginal VC: Appears as large, well-differentiated exophytic tumors, sometimes requiring reconstructive surgery after excision 2 8.

Clinical Behavior Across Types

All variants share key features:

• Slow, relentless local growth
• Low risk of lymph node or distant metastasis
• High risk of local tissue destruction if undiagnosed or untreated
• Frequent recurrence, especially if excision margins are not adequate 5 8 14

Causes of Verrucous Carcinoma

The causes of verrucous carcinoma are multifactorial, with several environmental, infectious, and lifestyle factors implicated in its development.

Cause	Mechanism/Contribution	Typical Sites Involved	Source(s)
Chronic inflammation	Prolonged irritation	Skin, mucosa	3 6 7 9
Human papillomavirus (HPV)	Oncogenic viral transformation	Oral, anogenital	7 8 9 10 13
Smoking	Carcinogen exposure	Oral, esophagus, skin	1 3 10 13
Alcohol consumption	Mucosal irritation/carcinogen	Oral, esophagus	1 3 10 13
Repeated trauma	Tissue injury, repair cycles	Skin, digits	6 9
Chemical exposure	Direct carcinogenesis	Skin, oral	9

Table 3: Major Causes and Risk Factors

Chronic Inflammation and Irritation

Chronic inflammation is a unifying theme in the development of verrucous carcinoma. Sites subject to long-standing irritation—such as chronic ulcers, scars, inflammatory sinuses, or mucosal inflammation from achalasia or esophagitis—are at increased risk 3 6 9.

Infectious Etiology: Human Papillomavirus (HPV)

There is strong evidence linking oncogenic HPV infection to verrucous carcinoma, especially in the oral and anogenital regions. HPV can induce malignant transformation in squamous epithelium, leading to the characteristic exophytic growth 7 8 9 10 13.

Lifestyle and Environmental Factors

• Smoking and Alcohol: Both are independently associated with increased risk, particularly for oral and esophageal forms 1 3 10 13. Smoking contributes to chronic mucosal irritation and carcinogen exposure.
• Repeated Trauma: Chronic mechanical injury, such as that from ill-fitting shoes or repeated trauma to the hands or feet, may predispose to verrucous carcinoma development in acral locations 6 9.
• Chemical Exposure: Contact with carcinogenic chemicals can also play a role, especially in occupational settings 9.

Multifactorial Nature

It's important to note that most cases result from a combination of these factors, rather than a single cause. Genetic mutations—such as SMARCA4 alterations in esophageal VC—are being explored but are not yet fully understood 1.

Treatment of Verrucous Carcinoma

Managing verrucous carcinoma requires a multidisciplinary approach, with surgery forming the cornerstone of treatment. Other modalities are considered based on tumor location, size, and recurrence risk.

Treatment Modality	Indication/Usage	Outcomes/Notes	Source(s)
Surgical excision	First-line, all sites	High local control, risk of recurrence if margins are inadequate	2 6 8 9 14
Mohs micrographic surgery	Recurrent/difficult sites	Lower recurrence, tissue-sparing	14
Chemosurgery	Oral, genito-gluteal, plantar	Complete ablation, maximal tissue preservation	12
Radiotherapy	Select cases, controversial	No clear increase in anaplastic transformation, may be effective	11 15
Endoscopic submucosal dissection	Early esophageal VC	Curative for small lesions	4
Lymph node dissection	Large or high-risk tumors	Often no nodal involvement	2
Reconstructive surgery	Extensive excisions	Functional/esthetic restoration	2

Table 4: Treatment Approaches

Surgical Excision: The Gold Standard

Wide local excision with clear margins is the primary treatment for most forms of verrucous carcinoma. Due to the tumor's tendency for local invasion and recurrence, excision must be thorough, and follow-up is essential 2 6 8 9.

• Mohs Micrographic Surgery: Particularly effective in recurrent cases or lesions located in anatomically challenging areas (e.g., foot, anogenital region). Mohs offers lower recurrence rates and maximizes tissue conservation 14.
• Amputation: May be necessary for advanced acral tumors with bone involvement, as in digital or plantar VC 9.

Chemosurgery

Chemoablative techniques, especially in oral, genito-gluteal, or plantar forms, allow for complete removal while preserving as much normal tissue as possible. Microscopically monitored ablation ensures completeness 12.

Radiotherapy: A Controversial Option

Historically, there have been concerns about anaplastic transformation (i.e., progression to a more aggressive cancer) following radiotherapy. However, recent studies indicate that radiotherapy can be effective without significantly increasing this risk, and it may be used in selected cases where surgery is not feasible or as adjuvant therapy 11 15.

Endoscopic and Minimally Invasive Techniques

In early-stage esophageal VC, endoscopic submucosal dissection is a promising curative option, allowing for complete removal with minimal morbidity 4.

Lymph Node Dissection and Reconstruction

Although lymph node metastasis is rare, lymphadenectomy may be performed in cases with suspicious nodes. Large excisions, especially in the vulva or oral cavity, may require reconstructive procedures to restore function and appearance 2.

Monitoring and Recurrence

Given the high risk of local recurrence, patients require regular follow-up—often every three months for the first year after surgery 8 9 14.

Conclusion

Verrucous carcinoma is a unique, well-differentiated variant of squamous cell carcinoma that, despite its slow progression, poses significant challenges due to its locally aggressive and recurrent nature. Early recognition, accurate diagnosis, and appropriate treatment are key to optimizing outcomes.

Key Points:

• Symptoms: Slow-growing, exophytic, wart-like masses; dysphagia and weight loss in esophageal cases; non-healing lesions in skin and oral forms.
• Types: Includes oral florid papillomatosis, epithelioma cuniculatum, Buschke-Löwenstein tumor, and more, classified by site.
• Causes: Multifactorial; chronic inflammation, HPV infection, smoking, alcohol, and trauma all play roles.
• Treatment: Surgery (excision or Mohs) is first-line; chemosurgery, radiotherapy, and endoscopic resection are considered in select cases. High recurrence risk necessitates diligent follow-up.

Awareness and multidisciplinary care are essential in managing this rare but impactful cancer type.