1 Pathology of oesophageal and gastric tumours Heike I. Grabsch Oesophagus oesophageal lesions, with dysphagia being the most common symptom. Bleeding due to a benign Introduction oesophageal tumour is rare and mostly related to secondary ulceration of the luminal surface. Leiomyoma is a smooth muscle (e.g. mesenchymal) Patients with malignant tumours of the oesophagus tumour first described by Virchow in 1867 and most commonly present clinically at an advanced surgically resected for the first time by Sauerbruch in disease stage with strictures, plaque-like lesions, 1932. Leiomyomas account for more than 50% of polypoid masses protruding into the lumen, diffuse all benign tumours of the oesophagus and are twice thickening of the mucosa and wall or deeply penetrating as frequent in males as in females. Leiomyomas ulcers. Oesophageal neoplasms can be broadly divided most commonly arise from the muscularis propria into epithelial and mesenchymal subtypes according to and are typically located in the distal or middle the cell of origin. Whilst epithelial neoplasms are much oesophagus. Most are less than 3 cm in size, form more common and can be recognised endoscopically a firm white-greyish mass and may be calcified. due to mucosal irregularities, mesenchymal neoplasms In contrast to gastrointestinal stromal tumours, are usually located in the submucosa with a normal leiomyomas are immunoreactive for desmin and overlying mucosa. smooth muscle actin and negative for c-KIT Precursor lesions of squamous cell cancers will (CD117) and DOG1(Discovered On GIST 1). be discussed in this chapter, together with their Developmental cysts and congenital oesophageal histopathological features as well as relevant duplications are the second most common benign molecular pathology. However, precursor lesions lesions of the oesophagus. Inclusion cysts are located of oesophageal adenocarcinoma and molecular within the oesophageal wall at the height of the pathology of oesophageal adenocarcinoma are tracheal bifurcation and may cause compression of only briefly mentioned here as they are covered the neighbouring respiratory tract. Duplication cysts in depth in Chapter 15. Lymphoma, melanoma, share the muscularis propria with the oesophagus choriocarcinoma and secondary tumours (metastases) and can be lined by oesophageal or gastric mucosa. of the oesophagus are not discussed here. Although they are located extramurally and usually do not communicate with the oesophageal lumen, symptoms and complications may occur due to Benign tumours and tumour-like ulceration, haemorrhage and perforation requiring surgical intervention. lesions of the oesophagus and the Fibrovascular polyps are the commonest intraluminal gastro-oesophageal junction benign tumours of the oesophagus, representing 12% of all benign oesophageal tumours. They are usually Benign oesophageal tumours and tumour-like lesions located in the cervical oesophagus and are often 7 cm constitute about 1% of all clinically symptomatic or longer when they become symptomatic. To prevent 1 Chapter 1 possible complications such as regurgitation or even in the clinical routine to ensure clear separation of fatal asphyxia, fibrovascular polyps are usually high-grade dysplasia from invasive carcinoma for surgically removed. patient management. Squamous cell papillomas are rare (less than 1% Squamous cell carcinoma is per definition a of all benign oesophageal tumours) but nevertheless neoplasm that at least penetrates the epithelial represent the most frequent benign epithelial tumour basement membrane into the lamina propria. It is of the oesophagus. They are most commonly located the most common malignant epithelial tumour of in the lower third of the oesophagus, are exophytic the oesophagus worldwide and affects males two to with a warty surface, sessile or partly pedunculated, ten times more often than females, with an average well demarcated and measure usually less than 5 mm age between 50 and 60 years at time of diagnosis. in diameter. Related to its endoscopic/macroscopic There is a marked geographic and ethnic variation in appearance, the differential diagnosis of a verrucous incidence. Incidence rates are highest in Iran, China, squamous cell carcinoma may need to be excluded South America and Eastern Africa and are higher in histologically. Squamous cell papillomas have been African-Americans than Caucasian-Americans. related to human papilloma virus infection. Granular cell tumours of the gastrointestinal tract represent 5% of all granular cell tumours The aetiology and predisposing factors for oesophageal squamous cell carcinoma vary in the human body, 25% of which are located 3 in the oesophagus. Nearly two-thirds of these significantly among different regions in the world. tumours have been found in the lower third of the Tobacco-smoking, alcohol and hot beverages such oesophagus, where they arise in the submucosa as hot mate tea are major risk factors for oesophageal squamous cell carcinoma.4,5 as endoscopically pale yellow sessile or polypoid lesions covered by normal mucosa. Histologically, the tumour cells are uniform large, plump cells with Dietary factors such as low intake of fresh fruits eosinophilic granular cytoplasm that are periodic and vegetables and high intake of barbecued meat acid-Schiff (PAS) and S100 positive. The covering or pickled vegetables most likely play a role in squamous epithelium is often thickened and can the aetiology of squamous cell carcinoma. The show pseudoepitheliomatous hyperplasia, which role of human papilloma virus (HPV) infection may be misdiagnosed as squamous cell carcinoma if in the pathogenesis of oesophageal squamous cell only superficial biopsies are taken. carcinoma is still controversial at this moment in time. Patients with achalasia have an increased risk of developing squamous cell cancer6 as do patients Malignant tumours of the with coeliac disease,7 Plummer–Vinson syndrome oesophagus and the (also called Paterson–Kelly syndrome),8 tylosis (also called focal non-epidermolytic palmoplantar gastro-oesophageal junction keratoderma),9,10 previous ingestion of corrosive substances,11 Zenker’s diverticulum12 or after Squamous cell carcinoma ionising radiation.13 In the Asian population, Precursor lesions of squamous cell carcinoma polymorphisms in ALDH1B1 and ALDH2, both Oesophageal squamous cell carcinoma development genes encoding aldehyde dehydrogenases, are is believed to be a multistep process from normal associated with squamous cell carcinoma.14 squamous epithelium via intraepithelial neoplasia Oesophageal squamous cell carcinomas are (synonym: dysplasia) to invasive carcinoma found in the upper, middle and lower third of the based on findings in high-risk populations where oesophagus in a ratio of approximately 1:5:2. The dysplasia predates the development of carcinoma native (untreated) macroscopic appearance of the by approximately 5 years.1,2 Dysplasia is defined as tumour depends on the depth of tumour invasion the presence of unequivocal neoplastic cells within and is classified into four different types according the epithelium. Squamous cell dysplasia is classified to the Japanese Esophageal Society15 which is similar as ‘low-grade’ when architectural and cytological to the macroscopic classification of gastric cancer abnormalities are seen in the basal half of the (Fig. 1.1). Approximately 60% of squamous cell squamous epithelium with preserved maturation of carcinomas show an exophytic or fungating growth the upper half and as ‘high-grade’ when more than pattern (Fig. 1.2), 25% are ulcerative and 15% are the bottom half shows architectural and cytological infiltrative. abnormalities. Full-thickness dysplasia of the Squamous cell carcinomas can grow horizontally and squamous epithelium is referred to as ‘carcinoma in vertically. In the West, 60% of patients have carcinomas situ’ or ‘non-invasive carcinoma’ by some authors. that have invaded beyond the muscularis propria However, the use of the term ‘carcinoma in situ’ or and have regional lymph node metastases at the time ‘non-invasive carcinoma’ is strongly discouraged of diagnosis. In contrast, in Japan, up to 40% of all 2 Pathology of oesophageal and gastric tumours Figure 1.1 • (a) Borrmann classification for advanced oesophageal and gastric cancers. Type I: polypoid I with a broad base, may be superficially Type 0-I ulcerated. Type II: excavated ulcerated Protruding lesion with elevated borders, sharp margin with no definitive infiltration into adjacent mucosa. Type III: ulcerative, Type 0-IIa II diffusely infiltrating base. Type IV: superficial diffusely infiltrative thickening of the elevated wall (linitis plastica). (b) Murakami classification for early cancers. Type 0-IIb Type 0-II Modified from Japanese Gastric Superficial III superficial Cancer Association. Japanese flat classification of gastric carcinoma, 3rd English edition. Gastric Cancer Type 0-IIc 2011;14(2):101–12. superficial depressed IV Type 0-III Excavated a b a b c Figure 1.2 • Oesophageal squamous cell carcinoma located in the middle oesophagus. (a) Fresh oesophagectomy specimen with a polypoid exophytic tumour growth and a smaller flat (red-coloured) mucosal abnormality. (b) Lack of (dark) iodine staining in the abnormal areas. (c) Same specimen after fixation. Courtesy of Dr Tomio Arai, Tokyo, Japan. 3 Chapter 1 resected oesophageal carcinomas are superficial or early Tumours are usually very large before they 16 carcinomas involving mucosa and submucosa only. become clinically apparent. Microscopically,