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| Squamous Carcinoma of the Esophagus |
| Etiology •Examination of geographic areas of high incidence have identified a number of environmental factors strongly linked to the development of esophageal dysplasia and squamous carcinoma •In the United States and Europe alcohol and smoking •In China nitrosamine containing foods, fungal contamination of foods and vitamin and essential metal deficiency •There is also preliminary suggestions that HPV may play a role similar to the findings already demonstrated in squamous carcinoma of the cervix and larynx •Chronic esophagitis (non-reflux) whateveer the etiology also has a causative role •The only known genetic predisposition occurs in hereditary tylosis, an autosomal dominant symmetrical keratosis of the palms and soles •Because of the striking pockets of high incidence, it is possible that hereditary or racial predisposition may augment the carcinogenic effect of environmental factors |
| Pathogenesis •Invasive squamous carcinoma of the esophagus is the end result of a progression through increasingly severe degrees of dysplasia to carcinoma-situ to invasive carcinoma •The common link between many of the dietary and environmental factors is a chronic inflammatory state associated with increased turnover of cells •Increased turnover of epithelium has been associated with the development of dysplasia such as occurs in the cervix and colon in inflammatory bowel disease •The role of oncogenes, tumor suppressor genes and gene replication monitoring has not been clarified as it has for colon carcinoma, |
| Epidemiology •At least 5X more common is men with the male/female ratio varying markedly worldwide, probably representing the variable exposure to environmental factors •At least 4X more common in blacks in the U.S., with the incidence in blacks rising while the incidence in whites is stable or declining •A disease of older people with a mean age of onset of 60 yrs. which probably reflects the slow evolution of the dysplasia carcinoma sequence |
| General Gross Description •Invasive squamous carcinoma of the esophagus is distributed as follows: upper third 20%; middle third 50%; lower third 20% •The dysplastic phase may be grossly inapparent •The in-situ phase also may have minimal change •Invasive carcinoma in its early phase is flat, white, with minimal thickening of the mucosa •As the carcinoma grows it most commonly is exophytic forming an intraluminal mass •Obstruction in these cases is due to luminal obstruction by tumor •Some invasive tumors remain relatively flat and as they expand develop central necrosis •A minority of tumors spread primarily within the esophageal wall and extend rapidly into surrounding tissue •Obstruction in these last two types of growth are due to narrowing of the lumen by thickening of the esophageal wall •As they enlarge invasive tumors have a firm white surface which if they are extremely well differentiated may have a flakey consistency due to extensive keratinization |
| General Microscopic Description •Most esophageal squamous carcinomas are well or moderately well differentiated with typical features of squamous carcinoma including: keratin pearls; intercellular bridges; single cell keratinization; and a sheet-like growth pattern •Rare variants include verrucous carcinoma which is a warty exophytic extremely well differentiated tumor which is slow growing and has a better prognosis •Poorly differentiated squamous carcinoma is seen as well as spindle cell variants and rarely a combination of glandular and squamous carcinoma |
| Clinical Correlation •Dysphagia and recent weight loss are the two most common symptoms •Development of symptoms is insidious and most tumors are far advanced at the time of diagnosis •The trachea is the adjacent tissue most commonly involved and tracheoesophageal fistula is found in up to 30% of cases •These will have symptoms of aspiration such as pneumonia or coughing due to aspiration of mucus due to hypersalivation and aspiration of saliva •Other regional tissues involved are the bronchi and aorta •Primary therapy is surgery alone or chemotherapy and radiation sometimes combined with surgery •Overall 5yr survival is 5% in this country, with resectable cases reported to have up to 15-20% 5yr survival •At the time of diagnosis 70% of patients have involved lymph nodes and the course of the disease is usually rapid with mean survival of <1 year in untreated cases •The most common extrathoracic site of metastasis is the liver (70%) |
| References • Cotran RS, Kumar V, Robbins SL: Robbins Pathologic Basis of Disease. 5th ed. Philadelphia, W.B. Saunders, 1994, pp. 764-765 |
| Squamous Carcinoma of the Esophagus |
| Synopsis by: Martin Nadel, M.D. (T62000M80703)[371] |
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