Histological pattern of esophageal cancer at BP Koirala memorial cancer hospital in Nepal: a three year retrospective study

Correspondence: Dr. Chin Bahadur Pun, MD Department of Pathology BP Koirala Memorial Cancer Hospital, Chitwan, Nepal E-mail: chinbahadur@hotmail.com Background: The incidence of esophageal adenocarcinoma is increasing in trends. Squamous cell carcinoma is associated with tobacco and alcohol consumption. Adenocarcinoma is often associated with a history of gastroesophageal reflux disease and Barrett's esophagus. The aim of this study was to find out the histological pattern of esophageal cancer in one of the largest Cancer center in Nepal.

to precancerous lesion.Esophageal adenocarcinoma arises most frequently in Barrett's epithelium through a series of progressive degrees of dysplasia; from intestinal metaplasia, to low grade dysplasia, high grade dysplasia and subsequently to cancer. 7,8Infrequently adenocarcinoma originates from heterotrophic gastric mucosa in the upper esophagus or from submucosal glands.
Small cell carcinoma (SCC) represents 1% of esophageal tumors.It usually affect male over 50 years of age.The common site is lower esophagus.It appears to arise from same multipotent epithelial basal cells that produce SQC; both tumors often intermingle. 9Immunohistochemical reaction for neurone-specific enolase, synaptophysin and chromogranin usually are positive and represent diagnostic marker for SCC. 10 Undifferentiated carcinoma of the esophagus is rare but highly malignant tumor.
In the WHO classification, undifferentiated carcinoma is defined as a tumor that has no ductal or squamous epithelial structure to indicate definite differentiation.It does not include SCC. 11e aim of this study was to find out the histological pattern of esophageal cancer in one of the largest cancer center in Nepal.

MATERIALS AND METHODS
This was a retrospective study conducted in the department of pathology, BP Koirala Memorial Cancer Hospital in Bharatpur, Chitwan between January 2008 and December 2011.The study consisted of 106 (endoscopic biopsies=57, radical esophagectomy specimens=49)) cases of esophageal carcinoma.The Hematoxylin and Eosin stained sections in all cases were reviewed by the authors and diagnosis was confirmed.Immunohistochemical staining for synaptophysin and chromogranin A was performed by the avidin-biotin-peroxidase technique, using ABC staining kits (Vector Laboratories, CA), following vendor's instructions.Relevant clinical data were retrieved from computer database of the hospital.The distribution of age, sex, and location of tumors were analyzed.Statistical analysis was done by using SPSS version 17.0 for windows.

RESULTS
There were a total of 106 cases of esophageal carcinoma.Out of 106 cases, 57 (53.8) were males and 49 (46.2%) were females.The male to female ratio was1.2:1.The esophageal cancer was most common in the age group of 61-70 years, comprising 34% of total cases.The esophageal cancer was uncommon in less than 30 years or more than 80 years of age.The age distribution of esophageal carcinoma is shown in Table 1.

Gross findings
The gross findings in SQC were either exophytic or ulcerative lesion with deep irregular ulcers (fig.1).The  Figure1: Macroscopic appearance of SQC showing ulcerative growth pattern with elevated ulcer edges.adenocarcinoma in distal esophagus showed flat patches to nodular masses.All the tumors were solitary type.The location of esophageal carcinoma is shown in Table 2.

Histological pattern of esophageal cancer
Distal third of esophagus was the most common site for esophageal carcinoma, followed by middle esophagus and proximal esophagus.The maximum number of SQC was seen in middle esophagus (n=22) followed by distal (n=21) and proximal esophagus (n=14).Similarly the maximum number of adenocarcinoma was seen in distal esophagus (n=27) followed by middle esophagus (n=2).
The SCC showed diffuse infiltrating sheets and nests of small round/oval cells with minimal cytoplasm and hyperchromatic nuclei with fine granular chromatin.The tumor cells were positive for chromogranin and synaptophysin (fig.4C and 4D).The highest TNM stage grouping recorded in resected specimens was pT2N1MX (stage IIB).

DISCUSSION
In our study, there were 68(64.15%)cases of SQC, 33(31.13%)cases of adenocarcinoma including signet ring cell carcinoma, 4(3.76%) cases of undifferentiated carcinoma and 1(0.94%) case of SCC.The global histological pattern of disease has changed recently.The two major histological types, SQC and adenocarcinoma differ substantially in their underlying patterns of incidence and key etiologic factors.Data from USA showed a 30% drop in incidence of SQC between 1973 and 2002.Incidence of adenocarcinoma has increased 4-fold over the same period. 2ancer of the esophagus shows an increasing occurrence of adenocarcinoma in the lower third of the esophagus and is frequently associated with Barrett's esophagus. 12,13Thus the Incidence of esophageal adenocarcinoma arising in distal esophagus is increasing in trends.In contrast to those findings, we found SQC as the most common esophageal cancer.The most common site for SQC was middle esophagus followed by distal and proximal esophagus.It is likely that HPV infection plays a much more significant role in SQC carcinogenesis. 14Distal esophagus was the commonest site for adenocarcinoma.
The single case of SCC was found in middle esophagus.SCC possibly arises from same multipotent epithelial basal cells that produce SQC and both tumors often intermingle with each other. 9It is not always possible to differentiate SQC and SCC based on histomorphology only.Immunostaining for CK14 and CD56 help distinguish SCC from SQC. 15 The area with the highest reported incidence for esophageal cancer is in the belt from eastern Turkey through northeastern Iran, northern Afghanistan and southern Russia to northern China, where it has been directly linked to the preservation of food using nitrosamines. 16The ethnicity may influence esophageal cancer histology or ethnic background may place an individual at increased risk for certain types of esophageal cancer. 17Poor socio-economic status resulting in fewer intakes of fresh fruits, vegetables and fish in addition to heavy hookah smoking are suspected to be the major risk factors for the development of esophageal cancer. 18Other findings suggest that a diet rich in foods from animal origin and poor in foods containing vitamins and fiber increase esophageal cancer risk. 19Drinking hot tea, a habit common in Golestan province, northern Iran, was strongly associated with a higher risk of esophageal cancer. 20[23] Early detection of cancer is most important.The superficial esophageal cancer is commonly observed as a slight elevation or shallow depression on the mucosal surface.Macroscopically, the lesion can be flat, polypoidal or ulcerative.Endoscopy utilizing Lugol iodine spray may be of value in detecting early dysplastic lesion. 24When the tumor is confined to the mucosa or submucosa, the term superficial esophageal carcinoma is used irrespective of the presence of regional lymph node metastasis.Superficial carcinoma accounted for 10-20% of all resected carcinomas in Japan, whereas in Western countries, superficial carcinomas are much less frequently reported. 25Superficial esophageal carcinoma limited to the mucosa may be treated by endoscopic mucosa resection (EMR).The EMR is also indicated for high grade intraepithelial neoplasia.There is no previous report regarding the incidence of esophageal carcinoma in Nepal.This study possibly reflects the histological pattern of esophageal cancer in our population.
It is likely to provide valuable data from which the disease can be tracked and prevention effort may be developed.
Multi-center studies of esophageal cancer including demographic data in different geographical and ethnical background are necessary in the future.

Figure 4A :Figure 3B :
Figure 4A: Diffuse infiltrating sheets and nests of small, round to oval cells with densely hyperchromatic nuclei with fine and granular chromatin and scant cytoplasm.Crush artifact is evident (HE stain, X100)