J

Fig. 1.06 Primary squamous cell carcinoma (CA) of oesophagus with an intramural metastasis (M) near the oesophagogastric junction.

superficial carcinomas are much less frequently reported {543}. About 5% of superficial carcinomas that have invaded the lamina propria display lymph node metastases, whereas in carcinomas that invade the submucosa the risk of nodal metastasis is about 35% {1055}. For tumours that have infiltrated beyond the submucosa, the term advanced oeso-phageal carcinoma is applied. Intramural metastases. A special feature of oesophageal SCC is the occurrence of intramural metastases, which have been found in resected oesophageal specimens in 11-16% of cases {896, 987}. These metastases are thought to result from intramural lymphatic spread with the establishment of secondary intramural tumour deposits. Intramural metastases are associated with an advanced stage of disease and with shorter survival. Second primary SCC. Additionally, the occurrence of multiple independent SCC has been described in between 14 and 31% of cases, the second cancers being mainly carcinomas in situand superficial SCC {1154, 989, 1507}. Treatment groups. Following the clinical staging, patients are usually divided into two treatment groups: those with locore-gional disease in whom the tumour is potentially curable (e.g. by surgery, radiotherapy, multimodal therapy), and those with advanced disease (metastases outside the regional area or invasion of the airway) in whom only palliative treatment is indicated {606}. Oeso-phageal SCC limited to the mucosa may be treated by endoscopic mucosal resection due to its low risk of nodal metastasis. Endoscopic mucosal resection is also indicated for high-grade intraepithelial neoplasia. Tumours that have invaded the submucosa or those in more advanced tumour stages have

Fig. 1.06 Primary squamous cell carcinoma (CA) of oesophagus with an intramural metastasis (M) near the oesophagogastric junction.

more than 30% risk of lymph node metastasis, and endoscopic therapy is not indicated {465}. Additionally, clinical staging is performed in order to determine the success of treatment, e.g. following radio- and/or chemotherapy.

Tumour spread

The most common sites of metastasis of oesophageal SCC are the regional lymph nodes. The risk of lymph node metastasis is about 5% in carcinomas confined to the mucosa but over 30% in carcinomas invading the submucosa and over 80% in carcinomas invading adjacent organs or tissues {772}. Lesions of the upper third of the oesophagus most frequently involve cervical and mediastinal lymph nodes, whereas those of the middle third metastasise to the mediastinal, cervical and upper gastric lymph nodes. Carcinomas of the lower third preferentially spread to the lower mediastinal and the abdominal lymph nodes {28}. The most common sites of haematogenous metastases are the lung and the liver {1153, 1789}. Less frequently affected sites are the bones, adrenal glands, and brain {1551}. Recently, disseminated tumour cells were identified by means of immunostaining in the bone marrow of about 40% of patients with oesophageal SCC {1933}. Recurrence of cancer following oesophageal resection can be locoregional or distant, both with approximately equal frequency {1185, 1027}.

Histopathology

Oesophageal SCC is defined as the penetration of neoplastic squamous epithelium through the epithelial basement membrane and extension into the lamina propria or deeper tissue layers. Invasion commonly starts from a carcinoma in situ with the proliferation of rete-like projections of neoplastic epithelium that push into the lamina propria with subsequent dissociation into small carcinomatous cell clusters. Along with vertical tumour cell infiltration, usually a horizontal growth undermines the adjacent normal mucosa at the tumour periphery. The carcinoma may already invade intramural lymphatic vessels and veins at an early stage of disease. The frequency of lymphatic and blood vessel invasion increases with increasing depth of invasion {1662}. Tumour cells in lymphatic vessels and in blood vessels may be found progressively several centimetres beyond the gross

Fig. 1.07 Squamous cell carcinoma with transmural invasion. M, remaining intact mucosa.

tumour. The carcinoma invades the muscular layers, enters the loose fibrous adventitia and may extend beyond the adventitia, with invasion of adjacent organs or tissues, especially the trachea and bronchi, eventually with the formation of oesophagotracheal or oesophago-bronchial fistulae {1789}. Oesophageal SCC displays different microscopic patterns of invasion, which are categorised as 'expansive growth' or 'infiltrative growth'. The former pattern is characterized by a broad and smooth invasion front with little or no tumour cell dissociation, whereas the infiltrative pattern shows an irregular invasion front and a marked tumour cell dissociation. The degree of desmoplastic or inflammatory stromal reaction, nuclear polymorphism and keratinization is extremely variable. Additionally, otherwise typical oesophageal SCC may contain small foci of glandular differentiation, indicated by the formation of tubular glands or mucin-producing tumour cells {987}.

Verrucous carcinoma (ICD-O 8051/3)

This rare variant of squamous cell carcinoma {19} is histologically comparable to verrucous carcinomas arising at other sites {969}. On gross examination, its appearance is exophytic, warty, cauliflower-like or papillary. It can be found in any part of the oesophagus. Histologically, it is defined as a malignant papillary tumour composed of well differentiated and keratinized squamous epithelium with minimal cytological atypia, and pushing rather than infiltrating margins {2066}. Oesophageal verrucous carcinoma grows slowly and invades locally, with a very low metastasising potential.

Spindle cell carcinoma (ICD-O 8094/3)

This unusual malignancy is defined as a squamous cell carcinoma with a variable

Fig. 1.08 Squamous cell carcinoma invading thin-walled lymphatic vessels.

sarcomatoid spindle cell component. It is also known by a variety of other terms, including carcinosarcoma, pseudosarco-matous squamous cell carcinoma, polypoid carcinoma, and squamous cell carcinoma with a spindle cell component {1055}. Macroscopically, the tumour is characterized by a polypoid growth pattern. The spindle cells may be capable of maturation, forming bone, cartilage and skeletal muscle cells {662}. Alternatively, they may be more pleomorphic, resembling malignant fibrous histiocytoma. In the majority of cases a gradual transition between carcinomatous and sarcomatous components has been observed on the light microscopic level. Immunohisto-chemical and electron microscopic studies indicate that the sarcomatous spindle cells show various degrees of epithelial differentiation. Therefore, the sarcoma-

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