What are the other Names for this Condition? (Also known as/Synonyms)

• Esophageal Verrucous (Squamous) Carcinoma
• Oesophageal Verrucous (Squamous) Carcinoma
• Verrucous (Squamous) Carcinoma of Oesophagus

What is Verrucous (Squamous) Carcinoma of Esophagus? (Definition/Background Information)

• Squamous cell carcinoma (SCC) of esophagus is a highly-malignant tumor of the epithelium. The esophagus is a part of the upper gastrointestinal tract and is also known as the ‘food-pipe’
• The Verrucous (Squamous) Carcinoma of Esophagus is an extremely rare subtype of SCC of esophagus. The tumor is diagnosed under a microscope, on examination of the cancer cells by a pathologist, and the subtype is denoted based on the predominant histologic pattern observed. This sub-classification of the tumor is important, as it may dictate the type of treatment to be provided and its prognosis
• The risk factors for Verrucous (Squamous) Carcinoma of Esophagus include smoking and alcohol consumption, dietary habits that exclude fresh fruits and vegetables, chronic esophagitis, and certain genetic conditions
• The cause of the condition is generally unknown, but numerous genetic abnormalities and gene involvement are noted. Verrucous (Squamous) Carcinoma of Esophagus is observed at a higher incident rate in certain geographical areas such as parts of China, Central Asia, and South Europe
• Most tumors are diagnosed at a later stage (with involvement of lymph nodes and/or metastasis to other body sites). Superficial tumors may be painless and asymptomatic, while advanced cases present swallowing difficulties and chest and upper abdominal pain
• The treatment of choice is a surgical excision with clear margins followed by radiation therapy/chemotherapy. In case of spread of cancer to other regions, a combination of treatments may be considered by the healthcare provider
• The prognosis depends upon a set of several factors including the stage of the tumor, the extent of tumor spread, overall health of the patient, and many other factors. In general, the prognosis of Verrucous (Squamous) Carcinoma of Esophagus is difficult to predict

Who gets Verrucous (Squamous) Carcinoma of Esophagus? (Age and Sex Distribution)

• Verrucous (Squamous) Carcinoma of Esophagus is a highly-uncommon condition that is normally observed in middle-aged and older adults, over the age of 50 years. Although, individuals of a wide age range may be affected (including children)
• Both males and females are affected, though the condition is much more common in males

• All races and ethnic groups are at risk for the condition

• However, the geographical distribution varies from certain high-incidence areas (including parts of east China, north Iran, and Kazakhstan) to low-incidence areas (USA and Scandinavian countries)

What are the Risk Factors for Verrucous (Squamous) Carcinoma of Esophagus? (Predisposing Factors)

The risk factors for Verrucous (Squamous) Carcinoma of Esophagus include the following: (a combination of factors may be present in some individuals)

• Presence of precursor lesions, which are low-grade intraepithelial neoplasm (LGIEN), having lower risk for squamous cell carcinoma (SCC) of esophagus; and, high-grade intraepithelial neoplasm (HGIEN) having higher risk for esophageal SCC
• Presence of gastrointestinal conditions such as long-standing inflammation of the esophagus (chronic esophagitis), diverticular disease, GERD, and achalasia
• Smoking tobacco is a major risk factor: Chronic and heavy smokers show a much higher risk. Amplified risk is found with more the number of cigarettes smoked, duration of smoking, and smoking of high-tar, hand-rolled tobacco products
• Chewing tobacco (India and parts of Africa) and betel nuts
• Use of opium, mostly in parts of Central Asia
• Alcohol consumption is an important risk factor; the risk is not dependent on the type of alcoholic drink consumed
• Drinking hot mate (mah-teh) made of yerba leaves: It is a high risk factor in South American countries of Argentina, Brazil, and Uruguay. The risk is linked to higher temperatures of the beverage
• Diet: Lack of fresh vegetables and fruits, fish and fresh meat, dairy products; also, a high consumption of processed meat (such as barbecued meat)
• Nutritional deficiencies that include vitamins A, B1, B2, B6, and C, and minerals zinc and molybdenum
• Certain exotic foods: Pickled vegetables in parts of China and bracken fern in Japan have been linked to an increased risk for the carcinoma
• Foods contaminated by fungi
• Drinking contaminated water that contain animal and human wastes
• Radiation therapy for breast cancer (especially in women)
• Presence of certain genetic disorders such as Plummer-Vinson syndrome (PVS), celiac disease, achalasia, epidermolysis bullosa (a type of skin disorder)
• Association of SCC with familial palmoplantar keratoderma (focal, non-epidermolytic) is strongly noted

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Verrucous (Squamous) Carcinoma of Esophagus? (Etiology)

The exact cause of development of Verrucous (Squamous) Carcinoma of Esophagus is unknown. Numerous genetic defects and gene involvement are noted.

• The TOC gene (tylosis oesophageal cancer gene) is associated with inherited palmoplantar keratoderma. There may be an involvement of the CYGB gene too
• Mutations in TP53 occurs in precursor lesions (noted in 35-80% of the cases)
• Other genes include the FHIT, DLEC1, and DEC1 genes, and many other proto-oncogenes
• Among the Asian population - ALDH1B1 and ALDH2 gene involvement is reported, against a background of smoking and drinking

In general, it is known that cancers form when normal, healthy cells begin transforming into abnormal cells - these cancer cells grow and divide uncontrollably (and lose their ability to die), resulting in the formation of a mass or a tumor.

• Many cancer types are caused by genetic mutations. These can occur, due to inherited mutations, or mutations that occur due to environmental factors 
• The transformation of normally healthy cells into cancerous cells may be the result of genetic mutations. Mutations allow the cancer cells to grow and multiply uncontrollably to form new cancer cells
• These tumors can invade nearby tissues and adjoining body organs, and even metastasize and spread to other regions of the body

What are the Signs and Symptoms of Verrucous (Squamous) Carcinoma of Esophagus?

Verrucous (Squamous) Carcinoma of Esophagus may present the following signs and symptoms:

• Initial superficial tumor may be asymptomatic. It is slow-growing and locally-invasive
• When it is confined to the mucosal surface, it may present a tingling sensation - this can help detection on an upper GI endoscopic series
• Tumors are observed to grow outward from the surface (exophytic); it occurs as a wart-like tumor mass
• Advanced tumors may be classified as ulcerating type, fungating type, infiltrating type, or a combination of these types (mixed)
• Commonly observed symptoms for advanced cancer are swallowing difficulties, chest pain (retrosternal pain), upper abdominal pain (epigastric pain), narrowing of esophagus that can cause regurgitation or vomiting sensation
• Advanced tumors invade into the esophageal wall beyond the submucosal surface. Early stage is stage 0, when only the mucosal surfaces are involved (and may be the submucosal surfaces too)
• Site of the tumor: Most cases are observed in the middle-third section of the esophagus; next is the lower-third region, followed by the upper-third region
• Esophageal carcinomas spread up and down the food-pipe or around the GI tube. The spread during later stages occurs along the surface (expansively) or deeper into the tissue layers (infiltrative)
• Large tumors may cause a pressure effect by compressing adjoining structures and organs
• Large tumors may ulcerate and bleed and become painful
• Involvement of lymph nodes: When upper esophagus is affected, the neck lymph nodes are involved (cervical lymph nodes); while tumors arising in the middle and lower third portion of esophagus typically affect the lymph nodes of the mediastinum

How is Verrucous (Squamous) Carcinoma of Esophagus Diagnosed?

A diagnosis of Verrucous (Squamous) Carcinoma of Esophagus may involve the following:

• A thorough medical history and physical examination
• X-ray of the chest
• CT or MRI scan of the chest: For advanced cases and to check cancer growth and spread, including lymph node involvement
• Upper GI endoscopy: An endoscopic procedure is performed using an instrument called an endoscope, which consists of a thin tube and a camera. Using this technique, the radiologist can have a thorough examination of the insides of the upper gastrointestinal tract
• Endoscopic ultrasonography: During this procedure, fine needle aspiration biopsy (FNAB) can be performed on the affected area. This is a good technique for tumor detection, including tumor invasion parameters, and to know whether the nearby lymph nodes are affected
• Endocytoscopy: It is a non-invasive technique helpful for invasive carcinomas that are located superficially
• Early cancer lesions may be detected using narrow band imaging technique
• Barium swallow
• Whole body PET scans to determine how far the cancer has spread to other organ systems

Although the above modalities can be used to make an initial diagnosis, a tissue biopsy of the tumor is necessary to make a definitive diagnosis to begin treatment. The tissue for diagnosis can be procured in multiple different ways which include: 

• Fine needle aspiration (FNA) biopsy of the tumor: A FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor and the tumor may be misdiagnosed. Hence, a FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
• Core biopsy of the tumor 
• Open biopsy of the tumor

Tissue biopsy:

• A tissue biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
• Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies to assist in the diagnosis

Note: Esophageal carcinomas may be graded as well-differentiated, moderately-differentiated, poorly-differentiated or undifferentiated carcinomas. The use of tumor grading in predicting prognosis is unclear and controversial. Most Esophageal Verrucous (Squamous) Carcinomas are reportedly highly-differentiated.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Verrucous (Squamous) Carcinoma of Esophagus?

The complications of Verrucous (Squamous) Carcinoma of Esophagus may include the following:

• Ulceration of the tumor can lead to secondary infections of bacteria and fungus
• Compression of the underlying nerve, which can affect nerve function
• Severe obstruction of the food-pipe with pain, leading to difficulties in eating. This can lead to extreme weight loss due to malnutrition
• Perforation or rupture of the esophagus can lead to the formation of tracheoesophageal fistula, which in turn can cause aspiration pneumonia. This is a life-threatening condition
• Stricture formation of esophagus
• Vocal cord paralysis
• Lung infection leading to pneumonia
• The tumor can metastasize to the nearby/local lymph nodes; metastasis is noted only occasionally
• When metastasis occurs via blood, the sites involved are the lungs, bones, kidney, adrenal gland, liver, and central nervous system (rarely)
• Recurrence of the tumor is frequent following treatment
• Side effects of chemotherapy (such as toxicity) and radiation
• Damage to the muscles, vital nerves, and blood vessels, during surgery
• Post-surgical infection at the wound site is a potential complication

How is Verrucous (Squamous) Carcinoma of Esophagus Treated?

The treatment of Verrucous (Squamous) Carcinoma of Esophagus usually involves surgery, which is the first treatment option considered. It also includes a combination of radiation therapy and chemotherapy.

• When the tumor is confined to the esophageal surface, then endoscopic mucosal/submucosal resection (or surgical removal via endoscopy) is undertaken
• Esophagectomy or surgery to remove part (or all) of esophagus
• If the tumor has metastasized, then a combination of chemotherapy, radiation therapy, and invasive procedures may be used to treat the tumor
• Palliative care is provided for advanced cancer stages
• Follow-up care with regular screening and check-ups are very important and encouraged

Clinical trials: In advanced stages of cancer progression, there may be some newer treatment options currently on clinical trials, which can be considered for some patients depending on their respective risk factors.

How can Verrucous (Squamous) Carcinoma of Esophagus be Prevented?

Currently, there are no known methods to prevent Esophageal Verrucous (Squamous) Carcinoma occurrence. However, the risk for the condition may be lowered through the following considerations:

• Avoidance of smoking tobacco and alcohol consumption
• Consuming a diet that is rich in whole grains, vegetables, and fruits
• Correcting any nutritional imbalances through adequate vitamin and mineral supplementation
• Taking foods rich in vitamin D and calcium
• Physical activities and regular exercising
• Taking early and appropriate treatment for any gastrointestinal conditions
• If the carcinoma is associated with a genetic disorder, then genetic counseling and testing may be performed
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• In order to avoid a relapse or be prepared for a recurrence, the entire diagnosis, treatment process, drugs administered, etc. should be well-documented and follow-up measures initiated

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory, due to its metastasizing potential and possibility of recurrence. Often several years of active vigilance are necessary.

What is the Prognosis of Verrucous (Squamous) Carcinoma of Esophagus? (Outcomes/Resolutions)

• The prognosis of Verrucous (Squamous) Carcinoma of Esophagus is generally better than the prognosis of conventional squamous cell carcinomas
• Positive prognostic factors include overall health of the patient, high blood count, normal body weight, early stage at detection, good response to treatment (surgery and/or chemotherapy or radiation therapy)
• The spread of cancer is very important in dictating outcomes (observed along-with staging). Involvement of lymph node and blood vessels indicates a poor outcome
• The prognosis of Verrucous (Squamous) Carcinoma of Esophagus depends upon a set of several factors, which include: 
  • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Individuals with bulky disease may have a poorer prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical resectability of the tumor (meaning, if the tumor can be removed completely)
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur 
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • Progression of the condition makes the outcome worse
• An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
• The combination chemotherapy drugs used, may have some severe side effects (such as cardio-toxicity). This chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor

Additional and Relevant Useful Information for Verrucous (Squamous) Carcinoma of Esophagus:

The following DoveMed website links are useful resources for additional information:

http://www.dovemed.com/diseases-conditions/cancer/