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Squamous Carcinoma
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 are 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) whatever 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
•Examples:
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
•Examples:
Squamous Cell Carcinoma in situ x4 Squamous Cell Carcinoma in situ x10 Squamous Cell Carcinoma in situ x10 Squamous Cell Carcinoma in situ x20 Squamous Cell Carcinoma-in-situ x40
References

Cotran RS, Kumar V, Robbins SL: Robbins Pathologic Basis of Disease. 5th ed. Philadelphia, W.B. Saunders, 1994, pp. 764-765

For Most Current Information Search Medline at National Library of Medicine
This link will directly take you to the relevant new literature
Squamous Carcinoma
Synopsis by: Martin Nadel M.D. (T62000M80702)[451]
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