Page 577 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

Esophageal Tumors 563

pain or difficulty in swallowing, progressive weight loss,
chest pain, or vomiting. By the time symptoms and signs
appear, the tumor usually has spread to submucosal lym-
phatic vessels. As a result of the advanced stage at diagno-
sis, the overall 5-year survival rate is less than 25%. By
contrast, 5-year survival approximates 80% in the few
patients with adenocarcinoma limited to the mucosa or
submucosa.

Squamous Cell Carcinoma AB

In the United States, esophageal squamous cell carcinoma Figure 14–12 Esophageal squamous cell carcinoma. A, Squamous cell
typically occurs in adults older than 45 years of age and carcinoma most frequently is found in the midesophagus, where it com-
affects males four times more frequently than females. Risk monly causes strictures. B, Squamous cell carcinoma composed of nests
factors include alcohol and tobacco use, poverty, caustic of malignant cells that partially recapitulate the stratified organization of
esophageal injury, achalasia, Plummer-Vinson syndrome, squamous epithelium.
frequent consumption of very hot beverages, and previous
radiation therapy to the mediastinum. It is nearly 6 times Most squamous cell carcinomas are moderately to well
more common in African Americans than in whites—a differentiated (Fig. 14–12, B). Less common histologic vari-
striking risk disparity that cannot be accounted for by dif- ants include verrucous squamous cell carcinoma, spindle cell
ferences in rates of alcohol and tobacco use. The incidence carcinoma, and basaloid squamous cell carcinoma. Regardless
of esophageal squamous cell carcinoma can vary by more of histologic type, symptomatic tumors are generally very
than 100-fold between and within countries, being more large at diagnosis and have already invaded the esophageal
common in rural and underdeveloped areas. The countries wall. The rich submucosal lymphatic network promotes cir-
with highest incidences are Iran, central China, Hong cumferential and longitudinal spread, and intramural tumor
Kong, Argentina, Brazil, and South Africa. nodules may be present several centimeters away from the
principal mass. The sites of lymph node metastases vary with
PATHOGE NESIS tumor location: Cancers in the upper third of the esophagus
favor cervical lymph nodes; those in the middle third favor
A majority of esophageal squamous cell carcinomas in Europe mediastinal, paratracheal, and tracheobronchial nodes; and
and the United States are at least partially attributable to the those in the lower third spread to gastric and celiac nodes.
use of alcohol and tobacco, the effects of which synergize to
increase risk. However, esophageal squamous cell carcinoma
also is common in some regions where alcohol and tobacco
use is uncommon. Thus, nutritional deficiencies, as well as
polycyclic hydrocarbons, nitrosamines, and other mutagenic
compounds, such as those found in fungus-contaminated
foods, have been considered as possible risk factors. HPV
infection also has been implicated in esophageal squamous
cell carcinoma in high-risk but not in low-risk regions. The
molecular pathogenesis of esophageal squamous cell carci-
noma remains incompletely defined.

MORPHOLOGY Clinical Features
Clinical manifestations of squamous cell carcinoma of the
In contrast to the distal location of most adenocarcinomas, esophagus begin insidiously and include dysphagia, ody-
half of squamous cell carcinomas occur in the middle third nophagia (pain on swallowing), and obstruction. As with
of the esophagus (Fig. 14–12, A). Squamous cell carcinoma other forms of esophageal obstruction, patients may unwit­
begins as an in situ lesion in the form of squamous dyspla- tingly adjust to the progressively increasing obstruction by
sia. Early lesions appear as small, gray-white plaquelike thick- altering their diet from solid to liquid foods. Extreme
enings. Over months to years they grow into tumor masses weight loss and debilitation result from both impaired
that may be polypoid and protrude into and obstruct the nutrition and effects of the tumor itself. Hemorrhage and
lumen. Other tumors are either ulcerated or diffusely infiltra- sepsis may accompany tumor ulceration. Occasionally, the
tive lesions that spread within the esophageal wall, where first symptoms are caused by aspiration of food through a
they cause thickening, rigidity, and luminal narrowing. These tracheoesophageal fistula.
cancers may invade surrounding structures including the
respiratory tree, causing pneumonia; the aorta, causing Increased use of endoscopic screening has led to earlier
catastrophic exsanguination; or the mediastinum and detection of esophageal squamous cell carcinoma. The
pericardium.