Carcinoma• Malignant neoplasms of epithelial cell origin,derived from any of the three germ layers,are called carcinomas.• Most esophageal tumors aremalignant, fewer than 1% arebenign.
Carcinoma of esophagusTwo morphologic variants :Adenocarcinoma andSquamous cell carcinoma.• Worldwide, squamous cell carcinoma is morecommon, but in the United States and otherWestern countries adenocarcinoma is on therise. . A general rule of thumb is that a cancer inthe upper two-thirds is a squamous cellcarcinoma and one in the lower one-third is anadenocarcinoma.
ADENOCARCINOMAAdenocarcinoma denotes a lesion in whichthe neoplastic epithelial cells grow inglandular patterns.Adenocarcinoma of the esophagus typicallyarises in a background of Barrett esophagusand long-standing GERD.
• Barrett esophagus is the only recognized precursorof esophageal adenocarcinoma. The developmentof AC from BE is a multistepprocess that unfoldsmany years.
The degree of dysplasia is the strongestpredictor of the progression to cancer.Individuals with low –grade dysplasia havevery low rates of progression AC but theprogression to cancer may be 10% or moreper year in individuals with high gradedysplasia.
•Overall, the risk fordeveloping AC varies from30-fold to more than100-fold above normal.
• In BE tissue there is increased cellproliferation, and chromosomalabnormalities become apparent in high-grade dysplasia. Mutations in p53progressively accumulate , and aneuploidy iscommonly found.
• Additional genetic abnormalities, such asalterations in HER-2/NEU and beta catenin,are present in the carcinomas but there areno specific markers that precisely identify thetransition from high-grade dysplasia to cancer.
Risk of adenocarcinomaBarrett esophaguAge- over 60Sex- more common in mendocumented dysplasiatobacco use,obesity,prior radiation therapy.ObesityWhites
Risk of adenocarcinoma is reduced by• diets rich in fresh fruits and vegetables.According to the National Cancer Institute,"diets high in cruciferous (cabbage,cauliflower,) and green and yellow vegetablesand fruits are associated with a decreased riskof esophageal cancer.
• Moderate coffee consumption is associated with adecreased risk.• According to one Italian study eating pizza more than oncea week .• Some Helicobacter pylori serotypes are associatedwith a decreased risk of adenocarcinoma, perhaps bycausing gastric atrophy and reducing acid reflux (reducedparietal cells).• NSAID, particularly aspirin.
Epidemiology• Esophageal adenocarcinoma occurs mostfrequently in Caucasians and sevenfold morecommon in men.• Rates being highest in certain developed Westerncountries, including the United States, the UnitedKingdom, Canada, Australia, the Netherlands, andBrazil and• Lowest in Korea, Thailand, Japan, and Ecuador.
• In countries where esophageal adenocarcinomais more common, the incidence hasincreased markedly since 1970, morerapidly than almost any other cancer. As aresult, esophageal adenocarcinoma, whichrepresented less than 5% of esophageal cancersbefore 1970, now accounts for halfof allesophageal cancers in the United States.
MorphologyEsophageal adenocarcinoma usually occurs inthe distal third of the esophagus andmay invade the adjacent gastric cardia.Initially appearing as flat or raised patchesin otherwise intact mucosa, large nodularmasses of 5 cm or more in diameter maydevelop. Alternatively, tumors may infiltratediffusely or ulcerate and invade deeply.
• Microscopically, Barrett esophagus is frequentlypresent adjacent to the tumor.• Tumors most commonly produce mucin and formglands, often with intestinal-type morphology;• less frequently tumors are composed of diffuselyinfiltrative signet-ring cells (similar to those seenin diffuse gastric cancers) or,• in rare cases, small poorly differentiated cells(similar to small-cell carcinoma of the lung).
• If the disease has spread elsewhere, thismay lead to symptoms related to this:liver metastasis could cause jaundice andascites,• lung metastasis could cause shortness ofbreath, pleural effusions, etc.
Treatment• The treatment is determined by the cellular typeof cancer (adenocarcinoma or squamous cellcarcinoma vs other types), the stage of thedisease, the general condition of the patient andother diseases present. On the whole, adequatenutrition needs to be assured, and adequatedental care is vital
Follow-up• Patients are followed up frequently after atreatment regimen has been completed.Frequently, other treatments are necessary toimprove symptoms and maximize nutrition.
Prognosis-Poor-dismal• By the time symptoms appear, the tumor hasusually spread to submucosal lymphaticvessels. As a result of the advanced stage atdiagnosis, overall 5-year survival is less than25%(15%) with most patients dying within thefirst year of diagnosis.• In contrast, 5-year survival approximates80% in the few patients withadenocarcinoma limited to the mucosa orsubmucosa.
Tylosis with esophageal cancerA genetic disorder characterized by thickening(hyperkeratosis) of the palms and soles, white patches inthe mouth (oral leukoplakia), and a very high risk ofesophageal cancer. This is the only genetic syndromeknown to predispose to squamous cell carcinoma of theesophagus. The risk of developing esophageal cancer is95% by age 70. The syndrome is inherited in an autosomaldominant manner. The gene has been mapped tochromosome 17q25 but has not been identified. Thesyndrome is also called nonepidermolytic palmoplantarkeratoderma. The association of tylosis palmoplantaris withesophageal cancer is called Howel-Evans syndrome.
Squamous cell carcinomaSquamous cell carcinomaa cancer in which the tumorcells resemble stratifiedsquamous epithelium.90% of esophageal cancer.
Risk factors of SCC of EsophagusI. Esophageal disorders:• Long standing esophagitis• Achalasia• Plummer-Vinson Syndrome
II. Life style:•Alcohol•Tobacco• An important contributing variable is retarded passage of food through the esophagus,prolonging mucosal exposure to potential carcinogens such as those contained in tobacco and alcohol beverages.• There is a well-defined predisposing role for chronic esophagitis, which is often the consequences of alcohol andtobacco use.
III. Dietary:• Def. of vit.• Def. of trace metals• Fungal contamination of food stuffs• High content of nitrites/nitrosamines• frequent consumption of very hotbeverages.
IV. Genetic predisposition:• Tylosis• Abnormalities affecting the p16/INK4 tumor suppressor gene and theepidermal growth factor receptors are frequently present in SCC of theesophagus. Mutation in p53 in 50% of these tumors.
V. Age. Over 45VI. Sex. males four times more frequently thanfemales.VII. PovertyVII. Race- more common in blacks (6 times)IX. Previous radiation therapy to themediastinum.X. HPVXI. Coeliac disease
• Esophageal squamous cell carcinomaincidence varies up to 180-fold between andwithin countries, being more common inrural and underdeveloped areas.• The regions with highest incidences are• Iran, central China, Hong Kong, Brazil, andSouth Africa.
PathogenesisThe majority of esophageal squamous cellcarcinomas in Europe and the United States are atleast partially attributable to the use of alcoholand tobacco, which synergize to increase risk.
• However, esophageal squamous cellcarcinoma is also common in some regionswhere alcohol and tobacco use isuncommon. Thus, nutritional deficiencies, aswell as polycyclic hydrocarbons,nitrosamines, and other mutageniccompounds, such as those found in fungus-contaminated foods, must be considered.
• Human papillomavirus (HPV) infection has alsobeen implicated in esophageal squamous cellcarcinoma in high-risk areas but not in low-riskregions.• The molecular pathogenesis of esophagealsquamous cell carcinoma remains incompletelydefined, but loss of several tumor suppressorgenes, including p53 and p16/INK4a, isinvolved.
Morphology•Epithelial dysplasia•Carcinoma in situ•Invasive cancer
• Early overt lesions appears as:small, gray-white, plaquelike thickenings orelevation of the mucosa.• In months to years these lesions becometumorous, taking one of three forms:
• 1. Polypoid exophytic masses that protrudeinto the lumen.• 2. Necrotizing cancerous ulceration that extenddeeply and sometimes erode into the respiratorytree (Pneumonia), aorta (exsanguination)( or elsewhere.• 3. Diffuse infiltrative neoplasm that causethickening and rigidity of the wall and narrowing ofthe lumen.
• SCC arise about:• 20% in the cervical& upper thoracic esophagus50% in the middle third• 30% in the lower third
Regardless of histology,symptomatic tumors are generallyvery large at diagnosis andhave already invaded the esophagealwall.
Prognosis- dismal• 5-year survival rates are 75% in individuals withsuperficial esophageal carcinoma but muchlower in patients with more advanced tumors.• Lymph node metastases, which are common,are associated with poor prognosis.• The overall 5-year survivalremains a dismal 9%.
Esophageal cancer. A, Adenocarcinoma usually occurs distally and, asin this case, often involves the gastric cardia. B, Squamous cellcarcinoma is most frequently found in the mid-esophagus, where itcommonly causes strictures.